JP2009531320A - Compounds that potentiate AMPA receptors and their use in medicine - Google Patents

Abstract

で示される化合物ならびにその塩および溶媒和物、さらに、その製造方法、医薬組成物および医薬としてのその使用、例えばグルタミン酸受容体機能の低下または不均衡により介在される疾患または症状、例えば統合失調症または認知機能障害の治療における使用に関する。The present invention relates to a compound of formula (I):

As well as salts and solvates thereof, as well as methods for their preparation, pharmaceutical compositions and their use as medicaments, such as diseases or conditions mediated by reduced or unbalanced glutamate receptor function, such as schizophrenia Or for use in the treatment of cognitive impairment.

Description

  The present invention relates to novel compounds that potentiate glutamate receptors. The invention also relates to the use of the compounds in the treatment of diseases and conditions mediated by potentiation of glutamate receptors, compositions containing the derivatives and methods for their preparation.

  Glutamate receptors that mediate most of the rapid excitatory neurotransmission in the mammalian central nervous system (CNS) are activated by the excitatory amino acid, L-glutamate (for example, Watkins JC, Krogsgaard- Larsen P, Honore T (1990) Trends Pharmacol Sci 11: 25-33).

  Glutamate receptors can be divided into two different families. The “metabolically regulated” glutamate receptor family bound to G-proteins or second messengers can be further divided into three groups based on sequence homology and intracellular transmission mechanisms (Group I, mGlu1 and mGlu5; Group II, mGlu2 and mGlu3; Group III, mGlu4, mGlu6, mGlu7, mGlu8) (For reports, see Conn PJ and Pinn JP (1997) Ann Rev Pharmacol Toxicol 37: 205-237). The “ion channel type” glutamate receptor family that binds directly to ligand-gated cation channels is a selective agonist, N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole. Based on depolarization activation by -4-propionic acid (AMPA) and kainic acid (KA), it can be further classified into at least three subtypes (for example, Dingledine R, Borges K, Bowie, Trainelis S ( 1999) 51: 7-61).

  The natural AMPA receptor (AMPAR) exists as a heterotetramer consisting of a combination of four different protein subunits (GluR1-4) (for the report, Bettler B and Muller C (1995) 34: 123- 139). Diversity of receptor subunits is further increased because each subunit may undergo alternative splicing of the 38 amino acid sequence in the extracellular region immediately preceding the 4-transmembrane domain M4 To do. Such editing results in so-called “flip” and “flop” receptor isoforms with different kinetic and pharmacological properties (Sommer B, Keinanen K, Verdon TA, Wisden W, Burnashhev N Herb A, Kohler M, Takagi T, Sakmann B, Seeburg PH (1990) Science 249: 1580-1585).

  In addition, post-transcriptional calibration of GluR2 mRNA changes neutral glutamine in M2 to positively charged arginine. In normal humans,> 99% GluR2 is calibrated in this way. AMPARs containing such calibrated GluR2 subunits exhibit low calcium permeability (Burnachev N, Monyer H, Seeburg PH, Sakmann B (1992) Neuron 8: 189-198). However, it has been suggested that the number of AMPARs with high calcium permeability is increased in symptoms associated with certain diseases (Weiss JH, and Sensi SL (2000) Trends in Neurosci 23: 365-371).

AMPAR depolarization removes the voltage-dependent Mg ²⁺ block of the NMDA receptor, which in turn leads to NMDA receptor activation, an essential step in the induction of long-term potentiation (“LTP”) (Bllis TVP, Collingridge GL (1993) Nature 361: 31-9). LTP is a physiological measure of increased synaptic strength after, for example, repetitive stimulation or activity as occurs during learning.

  Direct activation of glutamate receptors by agonists in a state of reduced glutamate receptor function has been reported to increase excitotoxicity and the risk of further neuronal damage. AMPAR positive allosteric modulators do not directly activate the receptor. However, when a ligand (L-glutamic acid or AMPA) is present, AMPAR modulators increase receptor activity. Thus, AMPA receptor modulators enhance synaptic function when glutamate is released and can bind to the postsynaptic receptor site. Various positive allosteric modulators have been studied in preclinical and clinical models of psychiatric disorders such as schizophrenia (Morrow JA, McLean J KF, Jameson C (2006) Current Opinion in Drug Discovery and Development 9 (5). -579).

Compounds acting as AMPAR positive allosteric modulators increase ligand affinity for the receptor (Arai A, Guidotti A, Costa E, Lynch G (1996) Neuroport. 7: 2211-5.); Receptor desensitization Reducing receptor deactivation (Arai AC, Kessler M, Rogers G, Lynch G (2000) 58: 802-813); in vitro (Arai A, Guidotti A, Costa E, Lynch G (1996). ) 7: 2211-5.) And in vivo (Staubri U, Perez Y, Xu F, Rogers G, Ingvar M, Stone-Elander S, Lynch G (1994) Proc Natl Acad Sci 91: 111. It has been shown to facilitate the induction of LTP in 8-11162) both. Such compounds may also be used in rodents (Zivkovic I, Thompson DM, Bertolino M, Uzunov D, DiBella M, Costa E, Guidotti A (1995) JPET 272: 300-309, Lebrun C, Pliere E, 2000). Eu J Pharmacol 401: 205-212), apes (Thompson DM, Guidotti A, DiBella M, Costa E (1995) Proc Natl Acad Sci 92: 76667671) and humans (Ingvar M, Ambros J, Ambros J Granger R, Kessler M, Rogers GA, Schehr RS, Lynch G (1997) Exp Ne. urol 146: 553-559) enhance learning and behavior of various cognitive tasks.
Watkins JC, Krogsgarard-Larsen P, Honore T (1990) Trends Pharmacol Sci 11: 25-33. Conn PJ and Pinn JP (1997) Ann Rev Pharmacol Toxicol 37: 205-237 Dingledine R, Borges K, Bowie, Trainelis S (1999) 51: 7-61 Bettler B and Muller C (1995) 34: 123-139 Somer B, Keinanen K, Verdonon TA, Wisden W, Burnashev N, Herb A, Kohler M, Takagi T, Sakmann B, Seeburg PH (1990) Science 249: 1580-1585. Burnachev N, Monyer H, Seeburg PH, Sakmann B (1992) Neuron 8: 189-198. Weiss JH, and Sensi SL (2000) Trends in Neurosci 23: 365-371 Bliss TVP, Collingridge GL (1993) Nature 361: 31-9 Arai A, Guidotti A, Costa E, Lynch G (1996) Neuroport. 7: 2211-5 Arai AC, Kessler M, Rogers G, Lynch G (2000) 58: 802-813 Arai A, Guidotti A, Costa E, Lynch G (1996) 7: 2211-5 Staubli U, Perez Y, Xu F, Rogers G, Ingvar M, Stone-Elander S, Lynch G (1994) Proc Natl Acad Sci 91: 11158-11162. Zivkovic I, Thompson DM, Bertolino M, Uzunov D, DiBella M, Costa E, Guidotti A (1995) JPET 272: 300-309 Lebrun C, Pillier E, Lestage P (2000) Eu J Pharmacol 401: 205-212 Thompson DM, Guidotti A, DiBella M, Costa E (1995) Proc Natl Acad Sci 92: 7667-7671) Ingvar M, Ambros-Ingerson J, Davis M, Granger R, Kessler M, Rogers GA, Schehr RS, Lynch G (1997) Exp Neurol 146: 553-559. Morrow JA, McLean J KF, Jameson C (2006) Current Opinion in Drug Discovery and Development 9 (5) 571-579

  Compounds that act as AMPAR positive allosteric modulators are known, for example, in international patent application WO2006 / 015828. JP 2001-220390 describes 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl] phenyl as a calcium channel inhibitor. ] -1,2,3-thiadiazole-5-carboxamide and its salts are disclosed. The present inventors have found a novel compound that also enhances the AMPA receptor.

［式中：
ｑは０または１であり；
ｎは０、１または２であり；
ＸはＣＲ^６Ｒ^７であり、Ｒ^６およびＲ^７は、各々独立して、水素、メチルおよびフルオロからなる群から選択される：ただし、Ｒ^６およびＲ^７は、両方同時にメチルではない；あるいは、ｎが１である場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、水素、Ｃ_２−４アルケニルおよびＣ_１−４アルキルからなる群から選択され；
ｍは０または１であり；
ａ）ｎが０であり、ｍが１である場合、Ｒ^１は、（ｉ）Ｃ_１−４アルキル、（ｉｉ）メチルにより置換されていてもよいＣ−結合５員の芳香族ヘテロサイクリック基、（ｉｉｉ）ＮＨＲ^２および（ｉｖ）ＮＲ^２’Ｒ^３からなる群から選択され、ここに：
Ｒ^２は、Ｃ_１−６直鎖アルキル、Ｃ_４−６分枝鎖アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚは、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；ここに、ＹがＣＯである場合、Ｒ^２は（ＣＨ_２）_２ピロリジニル以外であり；
Ｒ^２’は、メチルおよびエチルからなる群から選択され；
Ｒ^３は、Ｃ_１−６アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚ’は、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族または芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；あるいは
Ｒ^２’およびＲ^３は、それらが結合している窒素原子と一緒になって：
（ｉ）４または５員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、独立して、水素およびＣ_１−４アルキルからなる群から選択される）、ハロＣ_１−４アルキル、およびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；または
（ｉｉ）６員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、Ｃ_２−４アルキル、ハロＣ_１−４アルキルおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
を形成し；
ｂ）ｎおよびｍが、両方同時に０である場合、Ｒ^１は：
Ｃ_１−６アルコキシ；
炭素原子を介して結合する、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック基；
Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよいＮ−結合ピロリジニル；および
Ｃ_１−４アルキルにより置換されていてもよい、オキサゾリルまたはイミダゾリル；
からなる群から選択され；
ｃ）ｎが１または２であり、ｍが１である場合、Ｒ^１は、Ｃ_１−４アルキル、ベンジル、シクロプロピル、チエニルおよびＮＲ^９Ｒ^１０からなる群から選択され、ここに：
Ｒ^９は、水素およびＣ_１−４アルキルからなる群から選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック基または６員の非芳香族ヘテロサイクリック基を形成し、これらの環はいずれも、Ｃ_１−４アルキル、ハロ、フェニルおよび（非芳香環の場合）ケトからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
ｄ）ｎが１または２であり、ｍが０である場合、Ｒ^１は、シアノ、ヒドロキシ、ＮＨ_２、Ｃ−結合５員の芳香族ヘテロサイクリック基（Ｃ_１−６アルキルおよびＣ_３−６シクロアルキル、およびＮＲ^１１Ｒ^１２からなる群から独立して選択される１、２または３個の基により置換されていてもよい）からなる群から選択され、ここに：
Ｒ^１１は水素であり、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか；またはＲ^１１は、Ｃ_１−４アルキルおよびＣ_２−４アルケニルからなる群から選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、Ｃ（Ｏ）フェニルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか、または
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって：
（ｉ）５員の芳香族ヘテロサイクリック基（ここに、Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシ、Ｃ_３−６シクロアルキルおよびＣ_１−４アルコキシからなる群から独立して選択される１または２個の基により置換されていてもよい）；
（ｉｉ）フェニルにより置換されているイミダゾリル；
（ｉｉｉ）５員の非芳香族ヘテロサイクリック基（ここに、ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；および
（ｉｖ）６員の非芳香族ヘテロサイクリック基（ここに、ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
からなる群から選択される基を形成する］
で示される化合物またはその塩もしくは溶媒和物（ただし、４−メチル−Ｎ−［４−［４，５，６，７−テトラヒドロ−３−（トリフルオロメチル）−１Ｈ−インダゾール−１−イル］フェニル］−１，２，３−チアジアゾール−５−カルボキサミドおよびその塩を除く）を提供する。 In a first aspect, the present invention provides a compound of formula (I):

[Where:
q is 0 or 1;
n is 0, 1 or 2;
X is CR ⁶ R ⁷ and R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are not both methyl at the same time; or , When n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) a C-bonded 5-membered aromatic heterocyclic optionally substituted by methyl A group selected from the group consisting of (iii) NHR ² and (iv) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl; or R ^{2 '} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6 A membered non-aromatic heterocyclic group, wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl _{), C 2-4} alkyl, optionally substituted by one, two or three groups independently selected from the group consisting of halo _{C 1-4} alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2 and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² is a group consisting of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, Selected from the group consisting of C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are the nitrogen atom to which they are attached. With:
(I) a 5-membered aromatic heterocyclic group (wherein independent of the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups selected as above);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) And (iv) a 6-membered non-aromatic heterocyclic group (wherein substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); May be);
Forming a group selected from the group consisting of]
Or a salt or solvate thereof (provided that 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl] Phenyl] -1,2,3-thiadiazole-5-carboxamide and its salts).

The term “halo” means fluoro, chloro, bromo or iodo.
The term “C _1-6 alkyl” means an alkyl group having 1 to 6 carbon atoms; the term “C _1-4 alkyl” means an alkyl group having 1 to 4 carbon atoms. To do. Unless otherwise specified, C _1-4 alkyl or C _1-6 alkyl may be a linear or branched alkyl group. For example, the C _1-4 alkyl group is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl or t-butyl. The C _1-6 alkyl group may be selected from the group consisting of a C _1-4 alkyl group, sec-pentyl, n-pentyl, isopentyl, tert-pentyl and hexyl. For example, C _1-4 alkyl is methyl. The term “C _1-6 straight chain alkyl” refers to those in which the C _1-6 alkyl group is straight chain, such as methyl, ethyl, propyl, butyl, pentyl and hexyl. The term “C _4-6 branched alkyl” refers to those where the C _4-6 alkyl group is branched, eg, t-butyl. “Me” means methyl. “Et” means ethyl.
“Ph” means phenyl.

The term “C _1-4 alkoxy” refers to an —O—C _1-4 alkyl group wherein C _1-4 alkyl is as defined above.
The term “C _2-4 alkenyl” refers to a straight or branched chain hydrocarbon group containing 2 to 4 carbon atoms containing one or more carbon-carbon double bonds. Examples of such groups include ethenyl, propenyl and butenyl.
The term “C _3-6 cycloalkyl” refers to a cycloalkyl group consisting of 3 to 6 carbon atoms, ie, cyclopropanyl, cyclobutanyl, cyclopentanyl and cyclohexanyl.

The term “haloC _1-4 alkyl” means a C _1-4 alkyl group substituted by several fluorine, chlorine, bromine or iodine atoms, including mixtures thereof. Halo C _1-4 alkyl groups contain, for example, 1, 2 or 3 halogen atoms. For example, a halo C _1-4 alkyl group can replace all hydrogen atoms with halogen atoms. Examples of _{haloC1-4alkyl} groups include fluoromethyl, difluoromethyl and trifluoromethyl.

を意味する。 The term "3-membered carbocyclic ring" in the definition of R ⁶ and R ^7, the following group formed by R ⁶ and R ^7:

Means.

The term “C-bonded 5-membered aromatic heterocyclic group” in the definition of R ¹ when n is 0 and m is 1 is selected from the group consisting of nitrogen, oxygen and sulfur Means a C-linked aromatic heterocyclic group containing 2 or 3 heteroatoms. Examples include pyrrolyl, pyrrolinyl, pyrazolinyl, oxazolyl, isoxazoyl, imidazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, isothiazolyl, thiazolyl, triazolyl, furyl and thienyl.

  The terms “non-aromatic 5 or 6-membered heterocyclic group” and “aromatic or non-aromatic 5 or 6-membered heterocyclic group” in the definition of Z and Z ′ are derived from nitrogen, oxygen and sulfur. An aromatic or non-aromatic 5- or 6-membered group containing 1, 2 or 3 heteroatoms independently selected from the group consisting of Examples of aromatic vessels include: pyrrolyl, pyrazolinyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, isothiazolyl, thiazolyl, triazolyl, furyl, thienyl, pyridyl, thiazinyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl. Examples of non-aromatic vessels include pyrrolidinyl, pyrrolinyl, imidazolidinyl, pyrazolidinyl, isothiazolyl, thiazolyl, tetrahydrofuranyl, dioxolanyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydrothienyl, dioxanyl and dithianyl.

The term "non-aromatic heterocyclic group 4 or 5-membered" in the definition of R ² and R ^3, are formed by a nitrogen atom and R ² and R ³ wherein R ² and R ³ are attached 4 -Means a 5-membered non-aromatic ring, which ring may contain 1, 2 or 3 further heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. Examples include azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, isothiazolyl and thiazolyl.

The term "non-aromatic heterocyclic group 6-membered" in the definition of R ² and R ^3, it is formed by the ^'nitrogen atom and R ² which and R ³ are ^attached' and R ³ R 2 6 Means a member non-aromatic ring, which ring may contain 1, 2 or 3 additional heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. Examples include morpholinyl, thiomorpholinyl, piperidinyl and piperazinyl.
“CO” and “C (═O)” are interchangeable and refer to a carbonyl group. The term “keto” refers to the group ═O.

The term “monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group bonded via a carbon atom” in the definition of R ¹ when n and m are both 0 is Means a 5- or 6-membered ring attached through a carbon atom containing 1, 2 or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. Examples include pyrrolidinyl, pyrrolinyl, imidazolinyl, imidazolidinyl, piperidyl and morpholinyl.

In the definition of R ⁹ and R ^10, the term “5-membered aromatic or non-aromatic heterocyclic group” is defined by the nitrogen atom to which R ⁹ and R ¹⁰ are bonded and R ⁹ and R ^10. Means a membered aromatic ring or a 5-membered non-aromatic ring, which ring may contain 1, 2 or 3 additional heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In one embodiment, the heterocyclic group contains 0, 1 or 2 additional heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. Examples include pyrrolidinyl, imidazolidinyl, pyrazolidinyl, isothiazolyl, thiazolyl, pyrrolyl, pyrazolinyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, isothiazolyl, thiazolyl and triazolyl.

In the definition of R ⁹ and R ^10, the term “6-membered non-aromatic heterocyclic group” refers to a 6-membered non-ring formed by R ⁹ and R ¹⁰ and the nitrogen atom to which R ⁹ and R ¹⁰ are bonded. Means an aromatic ring, which ring may contain one or more additional heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In one embodiment, in one embodiment, the heterocyclic group contains 0, 1, 2, or 3 additional heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. Examples include piperidyl, piperazinyl, morpholinyl and thiomorpholinyl.

The term “C-bonded 5-membered aromatic heterocyclic group” in the definition of R ¹ when n is 1 or 2 and m is 0 is selected from the group consisting of nitrogen, oxygen and sulfur. Means a C-bonded aromatic heterocyclic group containing 1, 2 or 3 heteroatoms. Examples include pyrrolyl, pyrrolinyl, pyrazolinyl, oxazolyl, isoxazoyl, imidazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, isothiazolyl, thiazolyl, triazolyl, furyl and thienyl.

The term “5-membered aromatic heterocyclic group” in the definition of R ¹¹ and R ¹² when n is 1 or 2, m is 0 and R ¹ is NR ¹¹ R ¹² is R 5-membered aromatic heterocyclic group formed by the nitrogen atom to which ¹⁰ and R ¹¹ are bonded and R ¹⁰ and R ¹¹ (the ring is selected from the group consisting of nitrogen, oxygen and sulfur, 1, 2 Or it may contain 3 additional heteroatoms). Examples include pyrrolyl, pyrrolinyl, pyrazolinyl, oxazolyl, isoxazoyl, imidazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, isothiazolyl, thiazolyl and triazolyl.

The term “5-membered non-aromatic heterocyclic group” in the definition of R ¹¹ and R ¹² when n is 1 or 2, m is 0 and R ¹ is NR ¹¹ R ¹² is A 5-membered non-aromatic heterocyclic group formed by the nitrogen atom to which R ¹⁰ and R ¹¹ are bonded and R ¹⁰ and R ¹¹ (the ring is selected from the group consisting of nitrogen, oxygen and sulfur) Which may contain 2 or 3 additional heteroatoms). Examples include pyrrolidinyl, thiazolidinyl, imidazolidinyl, pyrazolidinyl and isothiazolidinyl.

The term “6-membered non-aromatic heterocyclic group” in the definition of R ¹¹ and R ¹² when n is 1 or 2, m is 0 and R ¹ is NR ¹¹ R ¹² is A 6-membered non-aromatic heterocyclic group formed by the nitrogen atom to which R ¹⁰ and R ¹¹ are bonded and R ¹⁰ and R ¹¹ (the ring is selected from the group consisting of nitrogen, oxygen and sulfur) Which may contain 2 or 3 additional heteroatoms). Examples include piperidyl, piperazinyl, morpholinyl and thiomorpholinyl.

Examples of compounds of formula (I) are:
N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-pyrrolidinylcarbonyl) phenyl ] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N- (phenylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamido N-ethyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl Benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl- -(2-Phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N, N-dimethyl-4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone 1 -[4- (Methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5, 6,7-Tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamido N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} a Cetamide N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-Phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1-{[4- (1 -Pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1-methyl-2-oxo-2- (1) -Pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3-oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pyrrolidinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H Indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetra Dro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N- Cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-thienylmethyl)- 2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl ) Acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl-N- ( {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-ethyl-N-({4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H-imidazol-1-yl) propyl] -N-methyl-4- [3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (2-thienyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1H-1,2,4-triazol-1-yl) ethyl] -4- [3- (trifluoromethyl)- , 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1,3-thiazol-2-ylmethyl) -4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1-methyl-1H-pyrrol-2-yl) ethyl] -4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] benzamide N- (2-furanylmethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-[(4-fluorophenyl) methyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4 -(4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4, 5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- {4- [1-fluoro-2-oxo-2- (1-pyrrolidi) L) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1,1-difluoro-2-oxo-2- (1-pyrrolidinyl) ) Ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- (4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] methyl} phenyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-y ] Phenyl} methyl) -1-pyrrolidinecarboxamide 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- (1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide N-methyl-N- (1- {4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide 1- [4- (1-acetyl-2-pyrrolidinyl) phenyl] -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydr B-1H-indazol-1-yl] phenyl} ethyl) -2-pyrrolidinone 1- {4-[(1,1-dioxide-2-isothiazolidinyl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 2-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) butanamide N-({4 -[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-thiophenecarboxamide N-({4- [ -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamido N-methyl-2-phenyl-N-({4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide N- (2-hydroxyethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] benzamido N-methyl-N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydride -1H-indazol-1-yl] benzamide N-methyl-N- [2- (methylamino) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole -1-yl] benzamido 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinol N-methyl -1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinamine 1- [4- (1 -Azetidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1-({4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-azetidinol (3,3-difluorocyclobutyl) {4- [3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazol-1-yl] phenyl} methanone 1- [4- (1H-imidazol-1-yl) phenyl] -3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N- (1-methylethenyl) -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ) -2-propenamide N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2 -Propenamide 1- {4-[(3-methyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole 1- {4-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazole N-ethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1-methyl Ethyl)- -[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-piperidinylcarbonyl) phenyl] -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole N, N-diethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Benzamide N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- {4- [2-oxo-2- (2) -Phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (to (Rifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide 1- [4- (1,3-oxazol-5-yl) phenyl] -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (propyloxy) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazole 1- [4- (1-methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propanesulfonamide N-({4- [3- Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide 1- [4- (1-pyrrolidinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazole N- (2-methylpropyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (4-morpholinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Dandazole N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- [2- (1-Pyrrolidinyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- (tetrahydro-2-furanylmethyl)- 4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (1H-imidazol-1-ylmethyl) phenyl] -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,4-triazol-1-ylme Til) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-pyrazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,3-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazole 1- [4- (2H-1,2,3-triazol-2-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H Indazole 1- {4-[(4-methyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Zole 1- {4-[(3,5-dimethyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 3- (Trifluoromethyl) -1- (4-{[3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 3- ( Trifluoromethyl) -1- (4-{[5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4 -{[5-Methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Sol 1- (4-{[3-methyl-5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole 1- {4-[(2-methyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1 -(4-{[2- (1-methylethyl) -1H-imidazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1 -{4-[(4-Phenyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [(4-Bromo-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-1H-imidazole-2- Yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone N-methyl-N- {4- [3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide and its salts and solvates thereof.

In one embodiment, the compound is:
N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-pyrrolidinylcarbonyl) phenyl ] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N- (phenylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamido N-ethyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl Benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl- -(2-Phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N, N-dimethyl-4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone 1 -[4- (Methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5, 6,7-Tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamido N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} a Cetamide N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-Phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1-{[4- (1 -Pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1-methyl-2-oxo-2- (1) -Pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3-oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pyrrolidinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H Indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetra Dro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N- Cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-thienylmethyl)- 2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl ) Acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl-N- ( {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-ethyl-N-({4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H-imidazol-1-yl) propyl] -N-methyl-4- [3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (2-thienyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1H-1,2,4-triazol-1-yl) ethyl] -4- [3- (trifluoromethyl)- , 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1,3-thiazol-2-ylmethyl) -4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1-methyl-1H-pyrrol-2-yl) ethyl] -4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] benzamide N- (2-furanylmethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide And N-[(4-fluorophenyl) methyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide Selected from.

In one embodiment, the compound is:
N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-pyrrolidinylcarbonyl) phenyl ] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N- (phenylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamido N-ethyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl Benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl- -(2-Phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N, N-dimethyl-4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone 1 -[4- (Methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5, 6,7-Tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamido N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} a Cetamide N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-Phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1-{[4- (1 -Pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1-methyl-2-oxo-2- (1) -Pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3-oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pyrrolidinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H Indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetra Dro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N- Cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-thienylmethyl)- 2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl ) Acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl-N- ( {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-ethyl-N-({4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H-imidazol-1-yl) propyl] -N-methyl-4- [3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (2-thienyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1H-1,2,4-triazol-1-yl) ethyl] -4- [3- (trifluoromethyl)- , 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1,3-thiazol-2-ylmethyl) -4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1-methyl-1H-pyrrol-2-yl) ethyl] -4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] benzamide N- (2-furanylmethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-[(4-fluorophenyl) methyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4 -(4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4, 5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide and its salts and solvates thereof

In one embodiment, the compound is:
1- {4- [1-Fluoro-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- { 4- [1,1-Difluoro-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl- N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- (4-{[3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl} phenyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl)- , 5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -1-pyrrolidinecarboxamide 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- (1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Ethyl) acetamide N-methyl-N- (1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide 1- [4- (1-acetyl-2-pyrrolidinyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (2- {4 [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) -2-pyrrolidinone 1- {4-[(1,1-dioxide-2- Isothiazolidinyl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 2-methyl-N-({4- [3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} methyl) butanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] pheny R} methyl) -2-thiophenecarboxamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N- ({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide N-methyl-2-phenyl-N-({4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide N- (2-hydroxyethyl) -N-methyl-4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (methyloxy) ethyl] -4- 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (methylamino) ethyl] -4- [3- (tri Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinol N-methyl-1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} carbonyl) -3-pyrrolidinamine 1- [4- (1-azetidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro 1H-indazole 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-azetidinol (3,3-difluoro Cyclobutyl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone 1- [4- (1H-imidazol-1-yl) Phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} methyl) -2-propenamide N- (1-methylethenyl) -N-({4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazol-1-yl] phenyl} methyl) -2-propenamide 1- {4-[(3-methyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-ethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1- L] benzamide N-methyl-N- (1-methylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4 -(1-Piperidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-diethyl-4- [3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1- Yl] benzamide 1- {4- [2-oxo-2- (2-phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahi B-1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide 1- [ 4- (1,3-oxazol-5-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (propyloxy) phenyl] -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1-methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Methyl) -2-propanesulfonamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide 1- [4- (1-pyrrole) Dinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N- (2-methylpropyl) -4- [3- (trifluoromethyl) -4, 5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (4-morpholinylsulfonyl) phenyl] -3- (to Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] benzenesulfonamide N- [2- (1-pyrrolidinyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1 -Yl] benzenesulfonamide N- (tetrahydro-2-furanylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (1H-imidazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazo 1- [4- (1H-1,2,4-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-pyrazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,3-triazole-1) -Ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (2H-1,2,3-triazol-2-ylmethyl) phenyl]- 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-methyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trif Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(3,5-dimethyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazole 3- (trifluoromethyl) -1- (4-{[3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4 , 5,6,7-tetrahydro-1H-indazole 3- (trifluoromethyl) -1- (4-{[5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4, 5,6,7-tetrahydro-1H-indazole 1- (4-{[5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trif Oromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[3-methyl-5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(2-methyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[2- (1-methylethyl) -1H-imidazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-phenyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl)- , 5,6,7-tetrahydro-1H-indazole 1- {4-[(4-bromo-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6 7-tetrahydro-1H-indazol N-methyl-1H-imidazol-2-yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Methanone N-methyl-N- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide and its salts and salts thereof Selected from the group consisting of solvates.

［式中：
ｑは０または１であり；
ｎは０、１または２であり；
ＸはＣＲ^６Ｒ^７であり、Ｒ^６およびＲ^７は、各々独立して、水素、メチルおよびフルオロからなる群から選択される：ただし、Ｒ^６およびＲ^７は、両方同時にメチルではない；あるいは、ｎが１である場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、水素、Ｃ_２−４アルケニルおよびＣ_１−４アルキルからなる群から選択され；
ｍは０または１であり；
ａ）ｎが０であり、ｍが１である場合、Ｒ^１は、（ｉ）Ｃ_１−４アルキル、（ｉｉ）メチルにより置換されていてもよいＣ−結合５員の芳香族ヘテロサイクリック基、（ｉｉｉ）ＮＨＲ^２および（ｉｖ）ＮＲ^２’Ｒ^３からなる群から選択され、ここに：
Ｒ^２は、Ｃ_１−６直鎖アルキル、Ｃ_４−６分枝鎖アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚは、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；ここに、ＹがＣＯである場合、Ｒ^２は（ＣＨ_２）_２ピロリジニル以外であり；
Ｒ^２’は、メチルおよびエチルからなる群から選択され；
Ｒ^３は、Ｃ_１−６アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚ’は、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族または芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；あるいは
Ｒ^２’およびＲ^３は、それらが結合している窒素原子と一緒になって：
（ｉ）４または５員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、独立して、水素およびＣ_１−４アルキルからなる群から選択される）、ハロＣ_１−４アルキル、およびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；または
（ｉｉ）６員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、Ｃ_２−４アルキル、ハロＣ_１−４アルキルおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
を形成し；
ｂ）ｎおよびｍが、両方同時に０である場合、Ｒ^１は：
Ｃ_１−６アルコキシ；
炭素原子を介して結合する、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック基；
Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよいＮ−結合ピロリジニル；および
Ｃ_１−４アルキルにより置換されていてもよい、オキサゾリルまたはイミダゾリル；
からなる群から選択され；
ｃ）ｎが１または２であり、ｍが１である場合、Ｒ^１は、Ｃ_１−４アルキル、ベンジル、シクロプロピル、チエニルおよびＮＲ^９Ｒ^１０からなる群から選択され、ここに：
Ｒ^９は、水素およびＣ_１−４アルキルからなる群から選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック基または６員の非芳香族ヘテロサイクリック基を形成し、これらの環はいずれも、Ｃ_１−４アルキル、ハロ、フェニルおよび（非芳香環の場合）ケトからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
ｄ）ｎが１または２であり、ｍが０である場合、Ｒ^１は、シアノ、ヒドロキシ、ＮＨ_２、Ｃ−結合５員の芳香族ヘテロサイクリック基（Ｃ_１−６アルキルおよびＣ_３−６シクロアルキル、およびＮＲ^１１Ｒ^１２からなる群から独立して選択される１、２または３個の基により置換されていてもよい）からなる群から選択され、ここに：
Ｒ^１１は水素であり、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか；またはＲ^１１は、Ｃ_１−４アルキルおよびＣ_２−４アルケニルからなる群から選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、Ｃ（Ｏ）フェニルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか、または
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって：
（ｉ）５員の芳香族ヘテロサイクリック基（ここに、Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシ、Ｃ_３−６シクロアルキルおよびＣ_１−４アルコキシからなる群から独立して選択される１または２個の基により置換されていてもよい）；
（ｉｉ）フェニルにより置換されているイミダゾリル；
（ｉｉｉ）５員の非芳香族ヘテロサイクリック基（ここに、ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；および
（ｉｖ）６員の非芳香族ヘテロサイクリック基（ここに、ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
からなる群から選択される基を形成する］
で示される化合物またはその塩もしくは溶媒和物（ただし、４−メチル−Ｎ−［４−［４，５，６，７−テトラヒドロ−３−（トリフルオロメチル）−１Ｈ−インダゾール−１−イル］フェニル］−１，２，３−チアジアゾール−５−カルボキサミドおよびその塩、または同時に、ｎ＝０、ｍ＝１、ｑ＝０、Ｙ＝ＣＯおよびＲ^１が、ＮＭｅ_２、ピロリジニル、ＮＭｅＣＨ_２Ｐｈ、モルホリニル、ピペリジル、ＮＨＥｔ、ＮＥｔ_２、ＮＨＭｅ、ＮＨＣＨ_２−テトラヒドロフラン−２−イル、ＮＨ（ＣＨ_２）_２Ｐｈ、ＮＨ（ＣＨ_２）Ｐｈ、ＮＨｔＢｕおよびＮＨ（ＣＨ_２）_３ＯＭｅからなる群から選択される化合物を除く）を提供する。 The invention also provides formula (A):

[Where:
q is 0 or 1;
n is 0, 1 or 2;
X is CR ⁶ R ⁷ and R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are not both methyl at the same time; or , When n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) a C-bonded 5-membered aromatic heterocyclic optionally substituted by methyl A group selected from the group consisting of (iii) NHR ² and (iv) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl; or R ^{2 '} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6 A membered non-aromatic heterocyclic group, wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl _{), C 2-4} alkyl, optionally substituted by one, two or three groups independently selected from the group consisting of halo _{C 1-4} alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2 and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² is a group consisting of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, Selected from the group consisting of C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are the nitrogen atom to which they are attached. With:
(I) a 5-membered aromatic heterocyclic group (wherein independent of the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups selected as above);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) And (iv) a 6-membered non-aromatic heterocyclic group (wherein substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); May be);
Forming a group selected from the group consisting of]
Or a salt or solvate thereof (provided that 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl] Phenyl] -1,2,3-thiadiazole-5-carboxamide and salts thereof, or simultaneously, n = 0, m = 1, q = 0, Y = CO and R ¹ are NMe ₂ , pyrrolidinyl, NMeCH ₂ Ph, morpholinyl, _{piperidyl, NHEt, NEt 2, NHMe,} NHCH 2 - _{tetrahydrofuran-2-yl, NH (CH 2) 2 Ph} , NH (CH 2) Ph, selected from NHtBu and NH _{(CH 2)} group consisting of 3 OMe (Excluding compounds).

Examples of compounds of formula (A) include:
N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-ethyl-N-methyl-4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] benzamide N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1 {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone 1- [4- (methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1-pyrrole) Nyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamido N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamido N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} acetamido N-methyl-N- (2-phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} acetamido 1-{[4- (1-pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1-Methyl-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N -Dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3-oxo-3 -(1-pyrrolidinyl) propyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pyrrolidinylca) Bonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] phenyl} acetamido N-cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Ndazol-1-yl] phenyl} acetamido N-methyl-N- (2-thienylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-i Ndazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} methyl) propanamide N-ethyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1 -({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5- {4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H-imidazol-1-yl) Propyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (2-thienyl) ) Ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (1H-1,2, 4-Triazol-1-yl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- (1, 3-thiazol-2-ylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide)
N-methyl-N- [2- (1-methyl-1H-pyrrol-2-yl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N- Methyl-N- (3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N- (2-furanylmethyl) -N- Methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-[(4-fluorophenyl) methyl] -N-methyl -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- {4- [1-fluoro-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1,1-difluoro-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (tri Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Zol-1-yl] phenyl} methyl) methanesulfonamide 1- (4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl} phenyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -1-pyrrolidinecarboxamide 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- (1- {4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamido N-methyl-N- (1- {4- [3- (trifluoro) Romethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide 1- [4- (1-acetyl-2-pyrrolidinyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Ethyl) -2-pyrrolidinone 1- {4-[(1,1-dioxide-2-isothiazolidinyl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazole 2-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) pro N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) butanamide N-({4- [3- (tri Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-thiophenecarboxamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1 -Yl] phenyl} methyl) acetamido N-methyl-2-phenyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Zol-1-yl] phenyl} methyl) acetamide N- (2-hydroxyethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1 -Yl] benzamide N-methyl-N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (methylamino) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1-({ 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinol N-methyl-1- ( {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinamine 1- [4- (1-azetidinyl) Carbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazol-1-yl] phenyl} carbonyl) -3-azetidinol (3,3-difluorocyclobutyl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazol-1-yl] phenyl} methanone 1- [4- (1H-imidazol-1-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahi Ro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N- ( 1-methylethenyl) -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N-methyl -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide 1- {4-[( 3-methyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [ (3-shi Ropropyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N- (1 -Methylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- {4- [2-oxo-2- (2- Phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide 1- [4- (1,3-oxazol-5-yl) phenyl] -3- (trifluoro (Romethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (propyloxy) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1 -[4- (1-Methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propanesulfonamide N-({4- [3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide N-({4- [3- (trifluoromethyl) -4,5,6 7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide 1- [4- (1-pyrrolidinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6 7-tetrahydro-1H-indazole N- (2-methylpropyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (4-Morpholinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N- [2- (methyloxy) ethyl] -4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- [2- (1-pi Lysinyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- (tetrahydro-2-furanylmethyl) -4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (1H-imidazol-1-ylmethyl) phenyl] -3- (tri Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,4-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4, 5,6,7-Tetrahydro-1H-indazole 1- [4- (1H-pyrazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4 , 5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,3-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazole 1- [4- (2H-1,2,3-triazol-2-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-Methyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [(3,5-Dimethyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 3- (trifluoro Til) -1- (4-{[3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 3- (trifluoromethyl ) -1- (4-{[5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[ 5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4 -{[3-Methyl-5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazo 1- {4-[(2-Methyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4 -{[2- (1-methylethyl) -1H-imidazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4 -[(4-Phenyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4- Bromo-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-1H-imidazol-2-yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone N-methyl-N- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide and its salts and solvates.

［式中、ｑ、ＹおよびＲ^１は、式（Ｉ）の記載と同意義である］
で示される化合物である（ただし、４−メチル−Ｎ−［４−［４，５，６，７−テトラヒドロ−３−（トリフルオロメチル）−１Ｈ−インダゾール−１−イル］フェニル］−１，２，３−チアジアゾール−５−カルボキサミドならびにその塩および溶媒和物は除く）。 In one embodiment, the compound of formula (I) is a compound of n = 0 and m = 1, which is represented by formula (Ia):

[Wherein q, Y and R ¹ are as defined in formula (I)]
(Wherein 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl] phenyl] -1, 2,3-thiadiazole-5-carboxamide and its salts and solvates are excluded).

In one embodiment, in formula (Ia), q is 0.
In one embodiment, in formula (Ia), Y is selected from the group consisting of CO, SO ₂ and NMeCO. In one embodiment, Y is CO or SO _2. In a further embodiment, Y is CO.
In one embodiment, in formula (Ia), R ¹ is C _1-4 alkyl.

In one embodiment, in formula (Ia), R ¹ is a C-bonded 5-membered aromatic heterocyclic group optionally substituted by methyl. In one embodiment, in formula (Ia), R ¹ is selected from the group consisting of pyrrolyl, pyrrolinyl, pyrazolinyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, oxadiazolyl, isothiazolyl, thiazolyl, triazolyl, furyl and thienyl, Each may be substituted with methyl. In one embodiment, in formula (Ia), R ¹ is imidazolyl optionally substituted by methyl.

In one embodiment, in formula (Ia), R ¹ is a NHR ² radical, wherein R ² is selected from the group consisting of C _1-6 straight chain alkyl and C _4-6 branched chain alkyl. The
In one embodiment, in formula (Ia), R ¹ is a NHR ² group, wherein R ² is selected from the group consisting of methyl and ethyl.
In one embodiment, in formula (Ia), R ¹ is an NHR ² group, wherein R ² is — (CH ₂ ) _p Z (wherein p is 1, 2 or 3 and Z is , Selected from the group consisting of hydroxy, methoxy and NHMe).

In one embodiment, in formula (Ia), R ¹ is an NHR ² group, wherein R ² is — (CH ₂ ) _p Z (wherein p is 1, 2 or 3 and Z is , Phenyl, imidazolyl, thienyl, triazolyl, thiazolyl, pyrrolyl, pyridyl, furanyl, pyrrolidinyl and tetrahydrofuranyl, each of which is from the group consisting of halo, C _1-4 alkyl and halo C _1-4 alkyl Optionally substituted by 1 or 2 independently selected groups; wherein when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl).

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ wherein R ^{2 ′} is methyl and ethyl; R ³ is selected from the group consisting of C _1-6 alkyl The
In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ , wherein R ^{2 ′} is selected from the group consisting of methyl and ethyl; R ³ is methyl, ethyl, propyl, Selected from the group consisting of isopropyl, butyl and t-butyl.
In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ , wherein R ^{2 ′} is selected from the group consisting of methyl and ethyl, and R ³ is — (CH ₂ ) _p Z A group wherein p is 1, 2 or 3 and Z 'is hydroxy, methoxy or NHMe.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ , wherein R ^{2 ′} is selected from the group consisting of methyl and ethyl, and R ³ is — (CH ₂ ) _p Z A group wherein p is 1, 2 or 3 and Z is selected from the group consisting of phenyl, imidazolyl, thienyl, triazolyl, thiazolyl, pyrrolyl, pyridyl, furanyl, pyrrolidinyl and tetrahydrofuranyl, each of which is , Optionally substituted by 1 or 2 groups independently selected from the group consisting of halo, C _1-4 alkyl and halo C _1-4 alkyl.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ , and R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
A 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently of the group consisting of hydrogen and C _1-4 alkyl; And optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
Pyrrolidinyl or azetidinyl, both of which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of halo, hydroxy, NR ¹³ R ¹⁴ , wherein R ¹³ and R ¹⁴ is independently selected from the group consisting of hydrogen and C _1-4 alkyl), halo C _1-4 alkyl, and keto)
Form.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
Pyrrolidinyl or azetidinyl, both of which may be substituted by 1 or 2 groups independently selected from the group consisting of hydroxy, NMe and fluoro
Form.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
A 6-membered non-aromatic heterocyclic group wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, haloC _1-4 alkyl and keto)
Form.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
Piperidyl, morpholinyl or piperazinyl (all of which are halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl), C Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _2-4 alkyl, haloC _1-4 alkyl and keto)
Form.

In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
Piperidyl, morpholinyl or piperazinyl (all of which are halo, hydroxy, NR ¹³ R ¹⁴ where R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl), C ₂ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl, halo C _1-4 alkyl and keto)
Form.

In a further embodiment, R ² and R ³ together with the nitrogen atom to which they are attached form a pyrrolidinyl ring, which is halo, C _1-4 alkyl, halo C _1-4 alkyl Or optionally substituted by one or more groups selected from keto. In one embodiment, R ² and R ³ together with the nitrogen atom to which they are attached form a pyrrolidinonyl or pyrrolidinyl ring.

In one embodiment, in formula (Ia), Y is CO and R ¹ is (i) a C-bonded 5-membered aromatic optionally substituted by C _1-4 alkyl and (ii) methyl. Selected from the group consisting of heterocyclic groups.
In one embodiment, in formula (Ia), Y is CO and R ¹ is selected from the group consisting of methyl, ethyl, and imidazolyl optionally substituted by one methyl.

In one embodiment, in formula (Ia), Y is CO and R ¹ is selected from the group consisting of NHR ² and NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl,

In one embodiment, in formula (Ia), Y is CO and R ¹ is a NHR ² group, where:
R ² is selected from the group consisting of C _1-6 straight chain alkyl and C _4-6 branched chain alkyl.
In one embodiment, in formula (Ia), Y is CO and R ¹ is a NHR ² group, where:
R ² is selected from the group consisting of methyl and ethyl.

In one embodiment, in formula (Ia), Y is CO and R ¹ is a NHR ² group, where:
R ² is — (CH ₂ ) _p Z (wherein p is 1, 2 or 3 and Z is hydroxy, methoxy or NHMe).

In one embodiment, in formula (Ia), Y is CO and R ¹ is a NHR ² group, where:
R ² is — (CH ₂ ) _p Z (wherein p is 1, 2 or 3 and Z is selected from the group consisting of phenyl, imidazolyl, thienyl, triazolyl, thiazolyl, pyrrolyl, pyridyl, furanyl and tetrahydrofuranyl) And each of these groups may be substituted by 1 or 2 groups independently selected from the group consisting of halo, C _1-4 alkyl and halo C _1-4 alkyl).

In one embodiment, in formula (Ia), Y is CO and R ¹ is NR ^{2 ′} R ³ where:
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is C _1-6 alkyl.

In one embodiment, in formula (Ia), Y is CO and R ¹ is NR ^{2 ′} R ³ where:
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is a — (CH ₂ ) _p Z ′ group, where p is 1, 2 or 3, and Z ′ is hydroxy, methoxy or NHMe.

In one embodiment, in formula (Ia), Y is CO and R ¹ is NR ^{2 ′} R ³ where:
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is a — (CH ₂ ) _p Z ′ group, where p is 1, 2 or 3, and Z ′ is phenyl, imidazolyl, thienyl, triazolyl, thiazolyl, pyrrolyl, pyridyl, furanyl, pyrrolidinyl and tetrahydrofuranyl. Each of these groups may be substituted by 1 or 2 groups independently selected from the group consisting of halo, C _1-4 alkyl and halo C _1-4 alkyl. ).

In one embodiment, in formula (Ia), Y is CO, R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
A 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently of the group consisting of hydrogen and C _1-4 alkyl; And optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto)
Form.

In one embodiment, in formula (Ia), Y is CO, R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
Pyrrolidinyl or azetidinyl (both of which are halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl), haloC _{1 -4} alkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto)
Form.

In one embodiment, in formula (Ia), Y is CO, R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
Pyrrolidinyl or azetidinyl, both of which may be substituted by 1 or 2 groups independently selected from the group consisting of hydroxy, NMe and fluoro
Form.

In one embodiment, in formula (Ia), Y is CO, R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
A 6-membered non-aromatic heterocyclic group wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, haloC _1-4 alkyl and keto)
Form.

In one embodiment, in formula (Ia), Y is CO, R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
Piperidyl, morpholinyl or piperazinyl (all of which are halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl), C Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _2-4 alkyl, haloC _1-4 alkyl and keto))
Form.

In one embodiment, in formula (Ia), Y is CO, R ¹ is NR ^{2 ′} R ³ and R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
Piperidyl, morpholinyl or piperazinyl (all of which are halo, hydroxy, NR ¹³ R ¹⁴ where R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl), C ₂ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl, halo C _1-4 alkyl and keto)
Form.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ and R ¹ is C _1-4 alkyl.
In one embodiment, in formula (Ia), Y is ^NR 8 CO, SO, an SO ₂ or ^NR 8 SO _2, ^{R 1} is methyl.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is an NHR ² group, wherein R ² is a C _1-6 straight chain Selected from the group consisting of alkyl and C _4-6 branched chain alkyl).
In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ and R ¹ is an NHR ² group, wherein R ² is t-butyl. is there.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is an NHR ² group, wherein R ² is — (CH ₂ ) _p Z (Wherein is 1, 2 or 3 and Z is hydroxy, methoxy or NHMe)).

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is an NHR ² group, wherein R ² is — (CH ₂ ) _p Z Wherein p is 1, 2 or 3, Z is phenyl or a 5 or 6 membered non-aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is an NHR ² group, wherein R ² is — (CH ₂ ) _p Z Wherein p is 1, 2 or 3, and Z is pyrrolidinyl or tetrahydrofuranyl).
In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is NR ^{2 ′} R ³ , wherein R ^{2 ′} is methyl and R ³ is selected from the group consisting of C _1-6 alkyl.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is NR ^{2 ′} R ³ , wherein R ^{2 ′} is methyl and Selected from the group consisting of ethyl; R ³ is selected from the group consisting of methyl and ethyl.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ and R ¹ is NR ^{2 ′} R ³ where:
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is — (CH ₂ ) _p Z (where p is 1, 2 or 3);
Z ′ is hydroxy, methoxy or NHMe.

In one embodiment, in formula (Ia), Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is NR ^{2 ′} R ³ , wherein:
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
Z ′ is phenyl or a 5- or 6-membered non-aromatic or aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from the group consisting of halo, C _1-4 alkyl and halo C _1-4 alkyl. It may be substituted by 1, 2 or 3 groups independently selected. In one embodiment, in formula (Ia), R ¹ is NR ^{2 ′} R ³ where:
R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached form azetidinyl, pyrrolidinyl, morpholinyl or piperidyl, which are each halo, hydroxy, NHMe, C _1-4 alkyl, halo It may be substituted by 1 or 2 groups independently selected from the group consisting of C _1-4 alkyl and keto.

［式中、ｑ、およびＲ^１は、式（Ｉ）の記載と同意義である］
で示される化合物である。 In one embodiment, the compound of formula (I) is a compound of n = 0 and m = 0, which is of formula (Ib):

[Wherein q and R ¹ are as defined in formula (I)]
It is a compound shown by these.

In one embodiment, in formula (Ib), q is 0.
In one embodiment, in formula (Ib), R ¹ is C _1-6 alkoxy. In one embodiment, R ¹ is methoxy, ethoxy or propoxy.

In one embodiment, in formula (Ib), R ¹ is substituted with 1 or 2 groups selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl and keto. Optionally N- or C-linked pyrrolidinyl. In one embodiment, R ¹ is 2-pyrrolidinonyl bonded through a nitrogen or carbon atom or N-methyl 2-pyrrolidinonyl bonded through a carbon atom.
In one embodiment, in formula (Ib), R ¹ is oxazolyl or imidazolyl, both of which may be substituted by methyl.

［式中、ｑ、ＹおよびＲ^１は、式（Ｉ）の記載と同意義である］
で示される化合物である。 In one embodiment, the compound of formula (I) is a compound of n = 1 or 2 and m = 1, which is of formula (Ic):

[Wherein q, Y and R ¹ are as defined in formula (I)]
It is a compound shown by these.

In one embodiment, in formula (Ic), q is 0.
In one embodiment, in formula (Ic), Y is selected from the group consisting of CO, NR ⁸ SO ₂ and NR ⁸ CO, wherein R ⁸ is hydrogen or C _1-2 alkyl. In one embodiment, Y is selected from the group consisting of CO, NHCO, NMeCO, NEtCO, NHSO ₂ and NMeSO ₂ .

In one embodiment, in formula (Ic), X is selected from the group consisting of CH ₂ , CHMe, CF ₂ and CR ⁶ R ⁷ , wherein R ⁶ and R ⁷ , the carbon to which they are attached. Together with the atoms, it forms a 3-membered carbocycle. In one embodiment, X is CH _2.
In one embodiment, in formula (Ic), R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl and thienyl.

In one embodiment, in formula (Ic), R ¹ is NR ⁹ R ¹⁰ where:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is selected from the group consisting of C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z. Wherein p is 1, 2 or 3, Z is phenyl or a 5- or 6-membered heterocyclic group, wherein the phenyl or heterocyclic group is a group consisting of halo and C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from

In one embodiment, in formula (Ic), R ¹ is NR ⁹ R ¹⁰ where:
R ⁹ is selected from the group consisting of hydrogen and methyl, R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3); and Z is phenyl or thienyl.

In one embodiment, in formula (Ic), R ¹ is NR ⁹ R ¹⁰ where:
R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached are 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and keto Forms a 5- or 6-membered non-aromatic heterocyclic group which may be substituted by

In one embodiment, in formula (Ic), R ¹ is NR ⁹ R ¹⁰ where:
R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached form a pyrrolidinyl or piperidyl ring, which is independent of the group consisting of C _1-4 alkyl, halo, phenyl and keto Optionally substituted by 1 or 2 groups.

In one embodiment, in formula (Ic), R ¹ is NR ⁹ R ¹⁰ where:
R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached form a pyrrolidinyl or piperidyl ring, both rings optionally substituted by 1 or 2 fluoro.

［式中、ｑ、ｎ、ＸおよびＲ^１は、式（Ｉ）の記載と同意義である］
で示される化合物である。 In one embodiment, the compound of formula (I) is a compound of n = 1 or 2 and m = 0, which is of formula (Id):

[Wherein q, n, X and R ¹ are as defined in formula (I)]
It is a compound shown by these.

In one embodiment, in formula (Id), q is 0.
In one embodiment, in formula (Id), the compound of formula (Id) is selected from the group consisting of CH ₂ , CHMe and (when n = 1) CR ⁶ R ⁷ , wherein , R ⁶ and R ⁷ are compounds that together with the carbon atom to which they are attached form a 3-membered carbocycle. In one embodiment, X is CH _2.

In one embodiment, n is 1 in formula (Id).
In one embodiment, in formula (Id), R ¹ is selected from the group consisting of cyano and hydroxy.

In one embodiment, in formula (Id), R ¹ is substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-6 alkyl and C _3-6 cycloalkyl. It may be a C-bonded 5-membered aromatic heterocyclic group. In one embodiment, R ¹ is oxadiazolyl optionally substituted by 1 or 2 groups independently selected from the group consisting of C _1-6 alkyl and C _3-6 cycloalkyl. In one embodiment, R ¹ is oxadiazolyl substituted with methyl or cyclopropyl.

In one embodiment, in formula (Id), R ¹ is an NHR ¹² group, wherein:
R ¹² is selected from the group consisting of SO ₂ C _3-6 cycloalkyl and C (O) C _2-4 alkenyl.
In one embodiment, in formula (Id), R ¹ is an NHR ¹² group, wherein:
R ¹² is selected from CO (CH═CH ₂ ) and SO ₂ -cyclopentanyl.

In one embodiment, in formula (Id), R ¹ is a NR ¹¹ R ¹² group, wherein:
R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4. Selected from the group consisting of alkenyl.

In one embodiment, in formula (Id), R ¹ is a NR ¹¹ R ¹² group, wherein:
R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is selected from the group consisting of COMe, C (O) phenyl and C (O) (CH═CH ₂ ). The

In one embodiment, in formula (Id), R ¹ is a NR ¹¹ R ¹² group, wherein:
R ¹¹ and R ¹² together with the nitrogen atom to which they are attached:
Pyrazolyl, imidazolyl and triazolyl, each of which may be substituted by 1 or 2 groups independently selected from the group consisting of C _1-4 alkyl, halo and halo C _1-4 alkyl; and Imidazolyl substituted by phenyl; and pyrrolidinyl or isothiazolidinyl (which may each be substituted by 1 or 2 keto, hydroxy and C _1-4 alkoxy); and piperidyl (keto, hydroxy and Optionally substituted by 1 or 2 groups independently selected from the group consisting of C _1-4 alkoxy)
Forming a group selected from the group consisting of

In one embodiment, in formula (Id), R ¹ is a NR ¹¹ R ¹² group, wherein:
R ¹¹ and R ¹² together with the nitrogen atom to which they are attached:
(I) pyrazolyl, imidazolyl and triazolyl, each of which may be substituted by 1 or 2 groups independently selected from the group consisting of methyl, isopropyl, halo and CF ₃ ; and (ii) Imidazolyl substituted by phenyl; and (iii) pyrrolidinyl or isothiazolidinyl (which may each be substituted by 1 or 2 keto); and (iv) piperidyl (substituted by keto) Also good)
Forming a group selected from the group consisting of

［式中：
ｑは０または１であり；
ｎは０、１、または２であり；
ＸはＣＲ^６Ｒ^７であり、ここに、Ｒ^６およびＲ^７は、各々、水素、メチルおよびフルオロからなる群から独立して選択される：ただし、Ｒ^６およびＲ^７は、両方同時にメチルではなく；または、ｎが１である場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、水素、Ｃ_２−４アルケニルおよびＣ_１−４アルキルからなる群から選択され；
ｍは０または１であり；
ａ）ｎが０であり、ｍが１である場合、Ｒ^１は、（ｉ）Ｃ_１−４アルキル、（ｉｉ）メチルにより置換されていてもよいイミダゾリル、（ｉｉｉ）ＮＨＲ^２および（ｉｖ）ＮＲ^２’Ｒ^３からなる群から選択され、ここに：
Ｒ^２は、Ｃ_１−６直鎖アルキル、Ｃ_４−６分枝鎖アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；ここに、ＹがＣＯである場合、Ｒ^２は（ＣＨ_２）_２ピロリジニル以外であり；
Ｒ^２’は、メチルおよびエチルからなる群から選択され；
Ｒ^３は、Ｃ_１−６アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚ’は、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族または芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
Ｒ^２’およびＲ^３は、それらが結合している窒素原子と一緒になって：
（ｉ）４または５員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、ハロＣ_１−４アルキル、およびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；または
（ｉｉ）６員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、Ｃ_２−４アルキル、ハロＣ_１−４アルキルおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
を形成し；
ｂ）ｎおよびｍが、両方同時に０である場合、Ｒ^１は：
Ｃ_１−６アルコキシ；
炭素原子を介して結合する、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック基；
Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよいＮ−結合ピロリジニル；および
Ｃ_１−４アルキルにより置換されていてもよい、オキサゾリルまたはイミダゾリル；
からなる群から選択され；
ｃ）ｎが１または２であり、ｍが１である場合、Ｒ^１は、Ｃ_１−４アルキル、ベンジル、シクロプロピル、チエニル、およびＮＲ^９Ｒ^１０からなる群から選択され、ここに：
Ｒ^９は、水素およびＣ_１−４アルキルからなる群から選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック基または６員の非芳香族ヘテロサイクリック基を形成し、これらの環はいずれも、Ｃ_１−４アルキル、ハロ、フェニルおよび（非芳香環の場合）ケトからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
ｄ）ｎが１または２であり、ｍが０である場合、Ｒ^１は、シアノ、ヒドロキシ、ＮＨ_２、Ｃ−結合５員の芳香族ヘテロサイクリック基（Ｃ_１−６アルキルおよびＣ_３−６シクロアルキル、およびＮＲ^１１Ｒ^１２からなる群から独立して選択される１、２または３個の基により置換されていてもよい）からなる群から選択され、ここに：
Ｒ^１１は水素であり、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、およびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか；または、Ｒ^１１は、Ｃ_１−４アルキルおよびＣ_２−４アルケニルからなる群から選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、Ｃ（Ｏ）フェニルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか、または
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって：
（ｉ）５員の芳香族ヘテロサイクリック基（Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシ、Ｃ_３−６シクロアルキルおよびＣ_１−４アルコキシからなる群から独立して選択される１または２個の基により置換されていてもよい）；
（ｉｉ）フェニルにより置換されているイミダゾリル；
（ｉｉｉ）５員の非芳香族ヘテロサイクリック基（ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
（ｉｖ）６員の非芳香族ヘテロサイクリック基（ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）
からなる群から選択される基を形成する］
で示される化合物またはその塩もしくは溶媒和物を提供する。 In one embodiment, the present invention provides compounds of formula (Ie):

[Where:
q is 0 or 1;
n is 0, 1, or 2;
X is CR ⁶ R ⁷ , wherein R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are both methyl at the same time Or, when n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) imidazolyl optionally substituted by methyl, (iii) NHR ² and (iv) Selected from the group consisting of NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl;
R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are from the group consisting of hydrogen and C _1-4 alkyl) (Optionally selected), optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6-membered A non-aromatic heterocyclic group of the above wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, halo C _1-4 alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2, and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl, and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² consists of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl, and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cyclo Selected from the group consisting of alkyl, C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are attached Together with the nitrogen atom:
(I) a 5-membered aromatic heterocyclic group (independently selected from the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy);
(Iv) 6-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy)
Forming a group selected from the group consisting of]
Or a salt or solvate thereof.

In one embodiment, in the formula (Ie), the compound at the same time, n = 0, m = 1 , q = 0, Y = CO and ^{R 1,} NMe _2, pyrrolidinyl, NMeCH ₂ Ph, morpholinyl, piperidyl _{, NHEt, NEt 2, NHMe,} NHCH 2 - _{tetrahydrofuran-2-yl, NH (CH 2) 2 Ph} , NH (CH 2) Ph, NHtBu and NH _{(CH 2)} 3 except compound selected from the group consisting of OMe It is.

［式中：
ｑは０または１であり；
ｎは０、１、または２であり；
ＸはＣＲ^６Ｒ^７であり、ここに、Ｒ^６およびＲ^７は、各々、水素、メチルおよびフルオロからなる群から独立して選択される：ただし、Ｒ^６およびＲ^７は、両方同時にメチルではない；または、ｎが１の場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、水素、Ｃ_２−４アルケニルおよびＣ_１−４アルキルからなる群から選択され；
ｍは０または１であり；
（ａ）（ｉ）ｎが０であり、ｍが１であり、ＹがＣＯである場合、Ｒ^１は、（ｉ）Ｃ_１−４アルキル、（ｉｉ）メチルにより置換されていてもよいＣ−結合５員の芳香族ヘテロサイクリック基、（ｉｉｉ）ＮＨＲ^２および（ｉｖ）ＮＲ^２’Ｒ^３からなる群から選択され；ここに：
Ｒ^２は、Ｃ_１−６直鎖アルキル、Ｃ_４−６分枝鎖アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
Ｒ^２’は、メチルおよびエチルからなる群から選択され；
Ｒ^３は、Ｃ_１−６アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚ’は、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族または芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；または
Ｒ^２’およびＲ^３は、それらが結合している窒素原子と一緒になって：
（ｉ）４または５員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、ハロＣ_１−４アルキル、およびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；または
（ｉｉ）６員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、Ｃ_２−４アルキル、ハロＣ_１−４アルキルおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
を形成し；
（ａ）（ｉｉ）ｎが０であり、ｍが１であり、ＹがＮＲ^８ＣＯ、ＳＯ、ＳＯ_２またはＮＲ^８ＳＯ_２である場合、Ｒ^１は、（ｉ）Ｃ_１−４アルキル、（ｉｉ）ＮＨＲ^２および（ｉｉｉ）ＮＲ^２’Ｒ^３からなる群から選択され、ここに：
Ｒ^２は、Ｃ_１−６直鎖アルキル、Ｃ_４−６分枝鎖アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
Ｒ^２’は、メチルおよびエチルからなる群から選択され；
Ｒ^３は、Ｃ_１−６アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚ’は、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族または芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；または
Ｒ^２’およびＲ^３は、それらが結合している窒素原子と一緒になって：
（ｉ）４または５員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、ハロＣ_１−４アルキル、およびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；または
（ｉｉ）６員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、Ｃ_２−４アルキル、ハロＣ_１−４アルキルおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
を形成し；
ｂ）ｎおよびｍが、両方同時に０である場合、Ｒ^１は：
Ｃ_１−６アルコキシ；
炭素原子を介して結合する、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック基；
Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよいＮ−結合ピロリジニル；および
Ｃ_１−４アルキルにより置換されていてもよい、オキサゾリルまたはイミダゾリル；
からなる群から選択され；
ｃ）ｎが１または２であり、ｍが１である場合、Ｒ^１は、Ｃ_１−４アルキル、ベンジル、シクロプロピル、チエニル、およびＮＲ^９Ｒ^１０からなる群から選択され、ここに：
Ｒ^９は、水素およびＣ_１−４アルキルからなる群から選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく、または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック基または６員の非芳香族ヘテロサイクリック基を形成し、該環はいずれも、Ｃ_１−４アルキル、ハロ、フェニルおよび（非芳香環の場合）ケトからなる群から独立して選択される１、２または３個の基により置換されていてもよく；および
ｄ）ｎが１または２であり、ｍが０である場合、Ｒ^１は、シアノ、ヒドロキシ、ＮＨ_２、Ｃ−結合５員の芳香族ヘテロサイクリック基（Ｃ_１−６アルキルおよびＣ_３−６シクロアルキル、およびＮＲ^１１Ｒ^１２からなる群から独立して選択される１、２または３個の基により置換されていてもよい）からなる群から選択され：ここに
Ｒ^１１は水素であり、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、およびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか；またはＲ^１１は、Ｃ_１−４アルキルおよびＣ_２−４アルケニルからなる群から選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、Ｃ（Ｏ）フェニルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか、または
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって：
（ｉ）５員の芳香族ヘテロサイクリック基（Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシ、Ｃ_３−６シクロアルキルおよびＣ_１−４アルコキシからなる群から独立して選択される１または２個の基により置換されていてもよい）；
（ｉｉ）フェニルにより置換されているイミダゾリル；
（ｉｉｉ）５員の非芳香族ヘテロサイクリック基（ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；および
（ｉｖ）６員の非芳香族ヘテロサイクリック基（ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
からなる群から選択される基を形成する］
で示される化合物またはその塩もしくは溶媒和物を提供する。 In one embodiment, the present invention provides compounds of formula (If):

[Where:
q is 0 or 1;
n is 0, 1, or 2;
X is CR ⁶ R ⁷ , wherein R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are both methyl at the same time Or when n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
(A) (i) when n is 0, m is 1 and Y is CO, R ¹ is (i) C _1-4 alkyl, (ii) C optionally substituted by methyl -Selected from the group consisting of a 5-membered aromatic heterocyclic group, (iii) NHR ² and (iv) NR ^{2 '} R ³ ;
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of ₄ alkyl; or R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are from the group consisting of hydrogen and C _1-4 alkyl) (Optionally selected), optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6-membered A non-aromatic heterocyclic group of the above wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, halo C _1-4 alkyl and keto);
Forming;
(A) (ii) when n is 0, m is 1, and Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is (i) C _1-4 alkyl, Selected from the group consisting of (ii) NHR ² and (iii) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of ₄ alkyl; or R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are from the group consisting of hydrogen and C _1-4 alkyl) (Optionally selected), optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6-membered A non-aromatic heterocyclic group of the above wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, halo C _1-4 alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2, and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl, and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached may be combined with a 5-membered aromatic or non-aromatic heterocyclic group or 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto And d) when n is 1 or 2, and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group ( _1-6 alkyl and _{C 3-6} cycloalkyl, and ^NR 11 optionally substituted by one, two or three groups independently selected from the group consisting of ^{R 12} is selected from the group consisting of may also be): Where R ¹¹ is hydrogen and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl, and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6. Selected from the group consisting of cycloalkyl, C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are Nitrogen field Together with:
(I) a 5-membered aromatic heterocyclic group (independently selected from the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); And (iv) a 6-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) ;
Forming a group selected from the group consisting of]
Or a salt or solvate thereof.

In one embodiment, in the above formula (If), the compound is simultaneously n = 0, m = 1, q = 0, Y = CO and R ¹ are: NMe ₂ , pyrrolidinyl, NMeCH ₂ Ph, morpholinyl, piperidyl _{, NHEt, NEt 2, NHMe,} NHCH 2 - _{tetrahydrofuran-2-yl, NH (CH 2) 2 Ph} , NH (CH 2) Ph, NHtBu and NH _{(CH 2)} 3 except compound selected from the group consisting of OMe It is.

［式中：
ｑは、０または１であり；
ｎは、０、１、または２であり；
ＸはＣＲ^６Ｒ^７であり、ここにＲ^６およびＲ^７は、各々独立して、Ｈ、ＭｅおよびＦから選択される：ただし、Ｒ^６およびＲ^７は、両方同時にＭｅではない；あるいは、ｎが１である場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、ＨおよびＣ_１−４アルキルから選択され；
ｍは、０または１であり；
および
ａ）ｎが０であり、ｍが１である場合：
Ｒ^１は、Ｃ_１−４アルキル、およびＮＲ^２Ｒ^３からなる群から選択され、ここに
Ｒ^２はＣＨ_３であり、Ｒ^３は、Ｃ_１−６直鎖アルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは、１、２または３である）から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルから選択される１個またはそれ以上の基により置換されていてもよく；または
Ｒ^２およびＲ^３は、それらが結合している窒素原子と一緒になって、５員の非芳香族ヘテロサイクリック環を形成し、該環は、ハロ、Ｃ_１−４アルキル、ハロＣ_１−４アルキル、およびケトから選択される１個またはそれ以上により置換されていてもよく；
ｂ）ｎおよびｍが両方とも同時に０の場合；
Ｒ^１は、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトから選択される１個またはそれ以上の基により置換されていてもよい、炭素原子を介して結合する、単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック環であり；
ｃ）ｎが１または２であり、ｍが１である場合
Ｒ^１は、Ｃ_１−４アルキルおよびＮＲ^９Ｒ^１０からなる群から選択され、ここに
Ｒ^９は、水素およびＣ_１−４アルキルから選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルから選択される１個またはそれ以上の基により置換されていてもよく；または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック環または６員の非芳香族ヘテロサイクリック環を形成し、これらはいずれも、Ｎ、ＯまたはＳから選択される１個またはそれ以上のさらなるヘテロ原子を含有していてもよく、Ｃ_１−４アルキル、ハロ、および（非芳香環の場合）ケトから選択される１個またはそれ以上の基により置換されていてもよく；
ｄ）ｎが１または２であり、ｍが０である場合
Ｒ^１は、シアノ、ＯＨ、ＮＨ_２およびＮＲ^１１Ｒ^１２からなる群から選択され、ここに
Ｒ^１１は、ＨおよびＣ_１−４アルキルから選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキルおよびＣ（Ｏ）Ｃ_１−４アルキルから選択されるか；あるいは
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって、５員の芳香族ヘテロサイクリック環、５員の非芳香族ヘテロサイクリック環および６員の非芳香族ヘテロサイクリック環から選択される基を形成し、これらはいずれも、Ｎ、ＯまたはＳから選択される１個またはそれ以上のさらなるヘテロ原子を含有していてもよく、５員の芳香族ヘテロサイクリック環は、Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシおよびＣ_１−４アルコキシから選択される１個またはそれ以上の基により置換されていてもよく；５員の非芳香族ヘテロサイクリック環は、ケト、ヒドロキシおよびＣ_１−４アルコキシから選択される１個またはそれ以上の基により置換されていてもよく；６員の非芳香族ヘテロサイクリック環は、ケト、ヒドロキシおよびＣ_１−４アルコキシから選択される１個またはそれ以上の基により置換されていてもよい］
で示される化合物またはその塩もしくは溶媒和物を提供する：ただし
同時にｎ＝０、ｍ＝０、ｑ＝０、およびＲ^１＝ＮＨ_２である化合物；
同時にｎ＝０、ｍ＝１、ｑ＝０、Ｙ＝ＣＯおよびＲ^１がＮＭｅＣＨ_２Ｐｈ、ピペリジニル、ピロリジニル、ＮＨ_２、Ｎ−メチルピペリジニル、ＮＭｅ_２およびモルホリニルから選択される化合物を除く。 The present invention also provides a compound of formula (I ′):

[Where:
q is 0 or 1;
n is 0, 1, or 2;
X is CR ⁶ R ⁷ where R ⁶ and R ⁷ are each independently selected from H, Me and F: provided that R ⁶ and R ⁷ are not both Me at the same time; when n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from H and C _1-4 alkyl;
m is 0 or 1;
And a) when n is 0 and m is 1:
R ¹ is selected from the group consisting of C _1-4 alkyl, and NR ² R ³ , wherein R ² is CH ₃ , R ³ is C _1-6 linear alkyl, C (O) C _{1 -4} alkyl and - _{(CH 2) (wherein,} p is 1, 2 or 3) p Z is selected from;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is one or more selected from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by a group; or R ² and R ³ together with the nitrogen atom to which they are attached form a 5-membered non-aromatic heterocyclic ring, which is a halo Optionally substituted by one or more selected from: C _1-4 alkyl, halo C _1-4 alkyl, and keto;
b) when n and m are both 0 at the same time;
R ¹ is a carbon, optionally substituted by one or more groups selected from C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic ring bonded through an atom;
c) when n is 1 or 2 and m is 1 R ¹ is selected from the group consisting of C _1-4 alkyl and NR ⁹ R ¹⁰ , wherein R ⁹ is hydrogen and C _1-4 alkyl R ¹⁰ is C _1-6 straight chain alkyl, C _3-6 cycloalkyl, C (O) C _1-4 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3) is selected from;
Z is phenyl or a 5 or 6 membered heterocyclic group, which phenyl or heterocyclic group may be substituted by one or more groups selected from halo and C _1-4 alkyl Well; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached form a 5-membered aromatic or non-aromatic heterocyclic ring or a 6-membered non-aromatic heterocyclic ring Each of which may contain one or more additional heteroatoms selected from N, O or S, C _1-4 alkyl, halo, and (if non-aromatic ring) keto Optionally substituted by one or more groups selected from:
d) when n is 1 or 2 and m is 0 R ¹ is selected from the group consisting of cyano, OH, NH ₂ and NR ¹¹ R ¹² , wherein R ¹¹ is H and C _1-4 Selected from alkyl and R ¹² is selected from SO ₂ C _1-4 alkyl and C (O) C _1-4 alkyl; or R ¹¹ and R ¹² together with the nitrogen atom to which they are attached. To form a group selected from a 5-membered aromatic heterocyclic ring, a 5-membered non-aromatic heterocyclic ring and a 6-membered non-aromatic heterocyclic ring, both of which are N , O or S, which may contain one or more further heteroatoms selected from C _1-4 alkyl, halo, halo C _1-4 alkyl , Hydroxy And optionally substituted by one or more groups selected from C _1-4 alkoxy; the 5-membered non-aromatic heterocyclic ring is selected from keto, hydroxy and C _1-4 alkoxy Optionally substituted by one or more groups; the 6-membered non-aromatic heterocyclic ring is substituted by one or more groups selected from keto, hydroxy and C _1-4 alkoxy. It may be]
Or a salt or solvate thereof: wherein n = 0, m = 0, q = 0, and R ¹ = NH ₂ at the same time;
At the same time excluding compounds where n = 0, m = 1, q = 0, Y = CO and R ¹ is selected from NMeCH ₂ Ph, piperidinyl, pyrrolidinyl, NH ₂ , N-methylpiperidinyl, NMe ₂ and morpholinyl.

  Descriptions of specific examples of any compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie) and (If) are given to each other and to formulas (A), (B) And the same applies to the compounds represented by (B ′).

  To avoid ambiguity, unless otherwise stated, the term substituted means substituted with one or more given substituents. In the case where a substituent may be selected from a number of other substituents, the selected substituents may be the same or different. To avoid ambiguity, the term independent means that when one or more substituents are selected from a number of possible substituents, the substituents may be the same or different. Means.

It will be apparent that the invention also includes compounds having any combination of the above groups.
In one embodiment, the salt or solvate of the compound of formula (I) is a pharmaceutically acceptable salt or solvate. In one embodiment, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof.

  The term “salt” as used herein refers to some salts, quaternary ammonium salts and internally formed salts of the compounds described in this invention prepared from inorganic or organic acids or bases. Pharmaceutically acceptable salts are particularly suitable for medical use because of their higher aqueous solubility compared to the parent compound. Such salts should clearly have a pharmaceutically acceptable anion or cation. Suitably, pharmaceutically acceptable salts of compounds of the invention include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, metaphosphoric acid, nitric acid and sulfuric acid, and tartaric acid, trifluoroacetic acid. Acetic acid, citric acid, malic acid, lactic acid, fumaric acid, benzoic acid, formic acid, propionic acid, glycolic acid, gluconic acid, maleic acid, succinic acid, (1S)-(-)-10-camphor sulfuric acid, (1S)- (+)-10-camphorsulfuric acid, isothionic acid, mucoic acid, gentisic acid, isonicotinic acid, sugar acid, glucuronic acid, furoic acid, glutamic acid, ascorbic acid, anthranilic acid, salicylic acid, phenylacetic acid, mandelic acid, embonic ) Acid (pamoic acid), methanesulfonic acid, ethanesulfonic acid, pantothenic acid, stearic acid, sulfinic acid, algin Acid addition salts formed with organic acids such as naphthalene-1,5-disulfonic acid, naphthalene-1,3-disulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid Base addition salts formed with alkali metals and alkaline earth metals and organic bases such as N, N-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine), lysine and procaine; And internally forming salts. Salts having non-pharmaceutically acceptable anions or cations are within the scope of the invention as intermediates useful for the preparation of pharmaceutically acceptable salts and / or for use in non-therapeutic, eg, in vitro situations. The salt may have some suitable stoichiometry. For example, the salt may have a 1: 1 or 2: 1 stoichiometry. Non-integer stoichiometric ratios can also occur.

  In addition, several crystalline forms of the compounds of formula (I) may exist as polymorphs and are encompassed by the present invention.

  Furthermore, some crystalline forms of the compounds of structure (I) may exist as polymorphs and are encompassed by the present invention. Some compounds of the invention may be crystallized or recrystallized from solvents such as aqueous and organic solvents. In such cases, solvates may be formed. The present invention includes within its scope stoichiometric solvates as well as compounds containing non-quantitative solvents, where non-stoichiometric solvents may be produced by processes such as lyophilization. In one embodiment, the compounds of the invention are obtained in the form of stoichiometric and non-stoichiometric hydrates.

  Certain protected derivatives of compounds of formula (I) that may be prepared before the final deprotection step may not have pharmacological activity per se, but in certain cases are administered orally or parenterally and then It will be apparent to those skilled in the art that it can be metabolized in the body to form pharmacologically active compounds of the present invention. Such derivatives may therefore be described as “prodrugs”. In addition, certain compounds of the present invention may be administered as prodrugs. Examples of prodrug forms for certain compounds of the present invention include Drugs of Today, Volume 19, November 9, 1983, pp 499-538 and Topics in Chemistry, Chapter 31, pp 306-316 and H.C. Bundgaard, Elsevier, “Design of Prodrugs”, 1985, Chapter 1 (disclosure of which is hereby incorporated by reference). In addition, certain moieties known to those skilled in the art as “pro-moieties” are described in, for example, H.P. As described in Bundgaard in “Design of Prodrugs” (the literature is incorporated herein by reference), such functional groups, when present in the compounds of the present invention, are placed on the appropriate functional groups. It will be apparent to those skilled in the art. Examples of prodrugs for certain compounds of the present invention include esters, carboxylic esters, hemiesters, phosphate esters, nitroesters, sulfate esters, sulfoxides, amides, carbamates, azo-compounds, phosphamides, glycosides, ethers, acetals And ketal.

  Certain compounds of formula (I) can exist in stereoisomers (eg, geometric isomers (or “cis-trans” isomers), diastereomers and enantiomers) and the present invention provides: Each of these stereoisomers is included, including mixtures thereof including racemates. Separate stereoisomers can be resolved from other isomers by conventional methods, or specific isomers can be obtained by stereoisomeric or asymmetric synthesis. The present invention also includes tautomers and mixtures thereof. The present invention includes within its scope all these isomers, including mixtures. It will be apparent that, like most biologically active molecules, biological activity can vary between the enantiomers of a particular molecule.

  In one embodiment, the chiral form of the compounds of the invention contains at least 80% e.e. e. Have In other embodiments, the chiral forms of the compounds of the invention contain at least 90% e.e. e. E.g., at least 95% e.e. e. Have In other embodiments, the isomers are at least 98% e.e. e, for example at least 99% e.e. matches e.

  Since the compounds of the invention are intended for use in pharmaceutical compositions, they are each in substantially pure form, such as at least 60% purity, such as at least 75% purity or at least 85%, or It will be readily appreciated that it can be provided with a purity of at least 98% (where% is based on weight). Impure compound preparations can be used to prepare the more pure forms used in pharmaceutical compositions; these less pure compounds of the invention are at least 1%, or at least 5% or 10%. Should contain -59% of a compound of the invention.

  The compounds of the present invention can be prepared in various ways. These processes form a further aspect of the present invention.

［式中、Ｘ’は脱離基であり、Ｘ、Ｙ、ｑ、ｍ、ｎおよびＲ^１は、式（Ｉ）の記載と同意義である］
で示される化合物と３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール

とをカップリングさせ；その後、任意に：
−いずれの保護基を除去すること；および／または
−式（Ｉｉ）で示される化合物またはその塩もしくは溶媒和物を、他の式（Ｉｉ）で示される化合物またはその塩もしくは溶媒和物に変換すること；
を含む方法を提供する。 The present invention also provides a process for producing a compound represented by the formula (I) or a salt or solvate thereof, wherein the formula (II):

[Wherein X ′ is a leaving group, and X, Y, q, m, n and R ¹ are as defined in the formula (I)]
And 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

And then optionally:
-Removing any protecting groups; and / or-converting a compound of formula (Ii) or a salt or solvate thereof into another compound of formula (Ii) or a salt or solvate thereof. To do;
A method comprising:

In the above reaction, for the compound of formula (I) where q is 0, X ′ may be, for example, a halogen such as bromine or iodine. Typical reaction conditions for compounds of formula (I) where q is 0 are compounds of formula (II), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H— Heating indazole, base (eg, potassium carbonate or cesium carbonate), copper (I) iodide or copper (I) oxide and N, N-dimethylglycine to 190 ° C. in a microwave reactor, or dimethyl Heat to 130 ° C. in sulfoxide, or heat trans-1,2-diaminocyclohexane in 1,4-dioxane at 180 ° C. in a microwave reactor, or (1R, 2R) —N, in toluene Heating N′-dimethyl-1,2-cyclohexanediamine at 130 ° C. in a microwave reactor. In one embodiment, (X) _n (Y) _m R ¹ is an acid, amide, ester, sulfonamide, ketone, urea, sulfone, alcohol, nitrile or heterocyclic group. 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole is commercially available. The compounds of formula (II) are either commercially available or can be prepared by methods described herein by conventional synthetic methods.

  In the above reaction, for the compound of formula (I) where q is 1, X ′ may be, for example, a halogen, such as bromine. Suitable reaction conditions for compounds of formula (I) wherein q is 1 are 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and compounds of formula (II) Of stirring in dimethylformamide with potassium carbonate at room temperature for 16 hours. The compounds of formula (II) are either commercially available or can be prepared by methods described herein by conventional synthetic methods. 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole) is commercially available.

A compound of formula (XIV) (ie, a compound of formula (II) wherein X, n and R ¹ are as defined in formula (I)) is prepared according to formula (XIII) ( In the formula, X, n and R ¹ can be prepared by iodination from a compound represented by the formula (I). Typical reaction conditions comprise heating a mixture of the compound of formula (XIII), iodine, periodic acid, water and concentrated sulfuric acid in acetic acid at 60 ° C. for about 6 hours. In one embodiment, X is methylene or methyl substituted methylene, R ¹ is NR ⁹ R ¹⁰ , wherein R ⁹ and R ¹⁰ are aliphatic groups, which may be the same or different, They may be linked to form a ring). The compounds of formula (XIII) are commercially available or can be prepared by methods described herein by conventional synthetic methods.

Useful for the preparation of the compound of formula (II), the compound of formula (XVII) is acylated from the compound of formula (XV) using the reagent of formula (XVI) according to reaction scheme 3. Or can be prepared by sulfonylation. Typical reaction conditions include reagent (XVI) in a cooled solution of (XV) in dichloromethane in the presence of a suitable base such as triethylamine or 1,8-diazabicyclo [5.4.0] undec-7-ene. Including dripping. In one embodiment, X is carbonyl or sulfonyl, R / Ar is aliphatic or aromatic, R ′ and R ″ are aliphatic (or may be hydrogen), They may be the same or different, or may be joined to form a ring. The compound represented by the formula (XV) is commercially available. Compounds of formula (XVI) are commercially available or can be prepared by methods analogous to those described in Scheme 11 below.

Useful for the preparation of the compound of formula (II), the compound of formula (XIX) is obtained by coupling the compound of formula (XVIII) with a secondary amine according to Reaction Scheme 4. Can be prepared. Typical reaction conditions include treating the compound of formula (XVII) with 1,1′-carbonyldiimidazole in dichloromethane, then adding the secondary amine and stirring at ambient temperature for a short time. (Bases such as triethylamine or diisopropylamine can also be added and should be amines available as acid salts). In one embodiment, R / Ar is aliphatic or aromatic and R ′ and R ″ are aliphatic groups, which may be the same or different and are bonded to form a ring. You may do it. The compound represented by the formula (XVIII) is commercially available.

Useful for the preparation of the compound of formula (II), the compound of formula (XXI) is prepared by alkylating a secondary amide or urea of formula (XX) with an alkyl halide according to Reaction Scheme 5. Can be prepared. Typical alkylation conditions are treatment of a compound of formula (XX) with a suitable base such as sodium hydride (available as a 60% suspension in mineral oil) in dimethylformamide, followed by alkyl Including adding an agent. In one embodiment, R ′ and R ″ are aliphatic (if it is an amide) and may be the same or different, may be joined to form a ring, or R 'Is aromatic and R ″ is an amine attached through a nitrogen atom (in the case of urea).

Useful for the preparation of compounds of formula (II), compounds of formula (XXXVI) are prepared by acylating secondary amines with compounds of formula (XXXV) according to reaction scheme 6. Can be prepared. Typical reaction conditions include adding a secondary amine to a solution of the compound of formula (XXXV) and a suitable base, such as triethylamine, and stirring at room temperature. In one embodiment, R ′ and R ″ are aliphatic and may be the same or different and may be joined to form a ring and R / Ar is aliphatic or aromatic A tribe. The compound represented by the formula (XXXV) is commercially available.

The compound represented by formula (XLII), which is useful for the preparation of the compound represented by formula (II), is obtained by converting the compound represented by formula (XL) into 4-chlorobutyryl chloride or 3-chloropropane according to Reaction Scheme 7. It can be prepared by acylation with sulfonyl chloride followed by alkylation. Typical conditions are treatment of a compound of formula (XL) and a suitable base such as triethylamine in dimethylformamide with 4-chlorobutyryl chloride or 3-chloropropanesulfonyl chloride followed by excess hydrogenation. Add sodium (60% suspension in mineral oil) and stir at room temperature until cyclization is complete. In one embodiment, R / Ar is aliphatic or aromatic and X is carbonyl or sulfonyl. The compound represented by the formula (XL) is commercially available. The compound represented by the formula (XLI) is commercially available.

Compounds of formula (IV) (ie n = 0, 1 or 2, X = CH ₂ , Y = CO, m = 1 and R ¹ = NR ² R ³ or R ¹ = NR ⁹ R ¹⁰ (wherein , R ² , R ³ , R ⁹ and R ¹⁰ are the same as described in formula (I)), the compound of formula (I) is represented by formula (V) according to Reaction Scheme 8 Can be prepared by coupling the compound to a secondary amine. Typical reaction conditions include treating the compound of formula (V) with 1,1′-carbonyldiimidazole in dichloromethane, then adding the secondary amine and stirring for 15 minutes at ambient temperature. Including. In one embodiment, R ² and R ³ , or R ⁹ and R ¹⁰ are aliphatic (or one is hydrogen) and may be the same or different to form a ring. It may be bonded.

A compound of formula (V), wherein q and n are as defined in formula (I), is represented by formula (X) according to reaction scheme 9, wherein q and n are those of formula (I) And R = alkyl, for example, C _1-6 alkyl). Typical reaction conditions involve heating a solution of the ester of formula (X) and sodium hydroxide in a 1: 1 mixture of water and ethanol to reflux for 1 hour. The compound represented by the formula (X) is prepared by a method similar to that described for the compound represented by the formula (I), that is, the compound represented by the formula (II) is converted into 3- (trifluoromethyl) -4,5. , 6,7-tetrahydro-1H-indazole).

A compound of formula (VI) (ie q = 0, X = CH ₂ , n = 1 or 2, Y = NR ⁸ CO, m = 1 and R ¹ and R ⁸ are as described in formula (I) A compound of the same significance and represented by formula (I) is prepared according to reaction scheme 10 by acylating a secondary amide of formula (VIII) with an alkyl of formula (VII) with a ride compound. can do. Typical alkylation conditions are treatment of a compound of formula (VIII) with a suitable base such as sodium hydride (available as a 60% suspension in mineral oil) in dimethylformamide, followed by alkyl Adding the agent (VII). In one embodiment, R ¹ and R ⁸ are aliphatic groups, which may be the same or different and may be linked to form a ring. The compound represented by the formula (VIII) is commercially available.

Compounds of formula (VII) can be prepared from benzyl alcohol of formula (IX) according to reaction scheme 11. Typical reaction conditions include treating a compound of formula (IX) with a suitable base, such as triethylamine, in dichloromethane, then adding methanesulfonyl chloride and stirring at room temperature for 18 hours. The compound represented by the formula (IX) is prepared by a method similar to the method described for the compound represented by the formula (I), that is, the compound represented by the formula (II) is 3- (trifluoromethyl) -4,5,6. , 7-tetrahydro-1H-indazole).

Compounds of formula (XII) (ie q = 1, n = 0, Y = CO, m = 1 and R ¹ = NR ² R ³ (wherein R ² and R ³ are Together with the nitrogen atom, forms a 4-, 5- or 6-membered non-aromatic heterocyclic group (shown as “G” in Scheme 12 below) having the same meaning as described in formula (I). According to Reaction Scheme 12, the compound represented by formula (I) is converted to 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole as an alkyl halide compound represented by formula (XI). It can be prepared by alkylation. Typical alkylation conditions include a microwave reactor at 140 ° C. with 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and (XI) together with potassium carbonate in dimethylformamide. Including heating for 10 minutes. Compounds of formula (XI) are commercially available or can be prepared from the corresponding acids by the methods described in Scheme 8.

A compound of formula (XXIII) can be prepared from a benzonitrile of formula (XXII) according to reaction scheme 13. Typical reaction conditions include treating a solution of lithium aluminum hydride in tetrahydrofuran with a compound of formula (XXII) in tetrahydrofuran with cooling, followed by stirring at room temperature for 1.5 hours. The compound of formula (XXII) is prepared by a method analogous to that for the compound of formula (I), ie the compound of formula (II) is converted to 3- (trifluoromethyl) -4,5, 6,7-tetrahydro-1H-indazole).

A compound of formula (XXVI) (ie n = 0, m = 1, Y = CO and R ¹ = NMe (CH ₂ ) p-Ar (wherein p is 1, 2 or 3 and Ar is The compound represented by the formula (I) which is phenyl or a 5- or 6-membered heterocyclic group having the same meaning as the formula (I)) is obtained by reacting the compound represented by the formula (XXIV) according to the reaction scheme 14. It can be prepared by coupling with a secondary amine. Typical reaction conditions are treatment of polymer-supported 1-ethyl-3- (dimethylaminopropyl) carbodiimide with a solution of 1-hydroxy-7-azaventtriazole in tetrahydrofuran: dichloromethane (1: 1) followed by benzoic acid. Add a solution of acid (XXIV) in N-methyl-2-pyrrolidinone: tetrahydrofuran (1: 3), then add a solution of amine (XXV) in dichloromethane and stir for 60 hours. In one embodiment, Ar is aromatic or heterocycle and n is 1, 2 or 3. The compound of formula (XXIV) is prepared in a manner analogous to that described for the compound of formula (I), ie the compound of formula (II) is converted to 3- (trifluoromethyl) -4,5, 6,7-tetrahydro-1H-indazole). The compound represented by the formula (XXV) is commercially available. Compounds of formula (XXIV) can be prepared by methods analogous to those described for compounds of formula (I).

Compound represented by formula (XXVII) (ie, n = 1 or 2, m = 0, X═CH ₂ and R ¹ ═NHR ¹² ′ (wherein R ^{12 ′} is SO ₂ C _1-4 alkyl, SO ₂ A compound of formula (I) which is C _3-6 cycloalkyl, C (O) C _1-4 alkyl, C (O) phenyl or C (O) C _2-4 alkenyl) is a reaction scheme According to 15, it can be prepared from a compound of formula (XXIII) by acylation or sulfonylation using a reagent of formula (XVI). Typical conditions include adding reagent (XVI) to a solution of (XXIII) in dichloromethane or 5-10% dimethylformamide in dichloromethane in the presence of a suitable base such as triethylamine. The compound represented by the formula (XVI) is commercially available.

Compound represented by formula (XXX) (ie, q = 0, n = 1, m = 1, Y = CO, X = CR ⁶ R ⁷ , wherein R ⁶ is fluorine and R ⁷ is hydrogen or fluorine R ¹ = NR ⁹ R ¹⁰ , wherein R ⁹ and R ¹⁰ are a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-cyclic group having the same meaning as described in formula (I) A compound of formula (I) which is an aromatic heterocyclic group) is fluorinated from a compound of formula (XXVIII) using a reagent of formula (XXIX) according to reaction scheme 16 Can be prepared. A typical condition is that a solution of the compound of formula (XXVIII) in tetrahydrofuran is added to a solution of lithium diisopropylamide in tetrahydrofuran at −78 ° C., followed by the addition of a fluorinating agent (XXIX) in tetrahydrofuran at room temperature. Stirring to obtain a mixture of R = H and R = F. The compound represented by the formula (XXVIII) is prepared by a method similar to that described for the compound represented by the formula (I), that is, the compound represented by the formula (II) is converted into 3- (trifluoromethyl) -4,5,6. , 7-tetrahydro-1H-indazole). The compound represented by the formula (XXIX) is commercially available.

A compound of formula (XXXIV) (i.e., n is a N-bond wherein q is 0 or 1, m and n are both 0, and R ¹ is substituted by ^one optionally substituted keto The compound of formula (I) which is pyrrolidinyl) can be prepared according to reaction scheme 17 by acylating the compound of formula (XXXIII) with 4-chlorobutyryl chloride. A solution of the compound of formula (XXXIII) and a suitable base such as diisopropylethylamine in dimethylformamide is treated with 4-chlorobutyryl chloride, followed by excess sodium hydride (60% suspension in mineral oil). ) And stirring at room temperature.

A compound of formula (XXXIII) can be prepared according to scheme 18 by reducing the compound of formula (XXXII) with sodium borohydride. Typical conditions include adding a compound of formula (XXXII) in methanol to a suspension of 10% palladium on carbon and sodium borohydride in water and stirring at room temperature for 1 hour.

A compound of formula (XXXIX) (ie, m is 0, n = 1 or 2, R ¹ is 1,2,4-oxadiazol-5-yl and R is C _1-6 alkyl or A compound of formula (I) that is C _3-6 cycloalkyl) can be prepared according to reaction scheme 19 by reacting a compound of formula (XXXVII) with an amidoxime of formula (XXXVIII) . Appropriate conditions are that 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride is added to a slurry of acid (XXXVII) and 1-hydroxybenzotriazole in acetonitrile, followed by the appropriate amidoxime after 30 minutes, Including heating to reflux. The compound represented by the formula (XXXVIII) is commercially available. The compound represented by the formula (XXXVII) can be prepared in the same manner as described for the compound represented by the formula (V) in Scheme 9.

Compound of formula (XLV) (ie q = 0, n = 0, m = 1, Y = CO and R ¹ optionally substituted by methyl C-bonded 5-membered aromatic heterocyclic The compound represented by the formula (I) is a 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole, 4-bromoiodobenzene and the formula (XLIV) according to the reaction scheme 20. ) In 3 steps. Typical reaction conditions include compound A in dimethyl sulfoxide in an advantageous heating process in the presence of 4-bromoiodobenzene and a base (eg, potassium carbonate), copper (I) iodide and N, N-dimethylglycine. Heating at 130 ° C. The product was then isolated and treated with n-butyllithium in tetrahydrofuran at −78 ° C. and then with a compound of formula (XLIV). 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and bromoiodobenzene are commercially available.

The compound of formula (XLIV) is a compound of formula (XLIII), wherein R1 ′ is a C-bonded 5-membered aromatic heterocyclic ring optionally substituted by methyl according to Reaction Scheme 21 Group) can be prepared by acylation with N, O-dimethylhydroxylamine hydrochloride. A typical acylation condition is HATU (O- (7-azabenzotriazol-1-yl) -N, N, N ′, N′-tetramethyluronium hexafluorophosphate), represented by formula (XLIII) Was added together with N, O-dimethylhydroxylamine hydrochloride and diisopropylamine (DIPEA) in dimethylformamide and stirred at room temperature for 17 hours. The compound represented by the formula (XLIII) is commercially available.

Compound represented by formula (XLVI) (where q is as defined in formula (I), n = 0, m = 1, Y = NHCO, and R ² R ³ is represented by formula (I) A 4-, 5-, or 6-membered non-aromatic heterocyclic group having the same meaning as described) is converted from the compound represented by the formula (XXIV) to the Curtius rearrangement and then the compound HNR ² R ³ according to Reaction Scheme 22. It can be prepared by reacting with. For example, HNR ² R ³ may be pyrrolidine. Typical reaction conditions include adding diphenylphosphoryl azide (DPPA) to a mixture of a compound of formula (XXIV) and diisopropylethylamine (DIPEA) in 1,4-dioxane. After stirring at reflux temperature for 2 hours, it was treated with HNR ² R ³ compound and reflux was continued for an additional hour. The compound represented by the formula (XXIV) is prepared by the same method as described for the compound represented by the formula (I), that is, the compound represented by the formula (II) is 3- (trifluoromethyl) -4,5,6,7. -Tetrahydro-1H-indazole).

Formula (XLVIII) (wherein q is as defined in formula (I), n = 1 or 2, m = 0 and R ¹ is an NR ¹¹ R ¹² group (where R ¹¹ and R ¹² are Substituted by 1 or 2 groups independently selected from the group consisting of: C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy. An optionally selected 5-membered aromatic heterocyclic group; or imidazolyl substituted by phenyl, or substituted by at least one keto and independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy Which is a 5- or 6-membered non-aromatic heterocyclic group optionally substituted by one or two other groups, According 23, wherein (XLVII) ^{(here, R 11} and ^{R 12} has the formula (as defined herein for XLVIII)) a heterocyclic group represented by benzyl chloride compound represented by the formula (VII) It can be prepared by alkylation. Typical alkylation conditions are treatment of a compound of formula (XLVII) with a suitable base such as sodium hydride (available as a 60% suspension in mineral oil) in dimethylformamide, followed by alkylation. Adding agent (VII). In one embodiment, NR ¹¹ R ¹² is an imidazolyl, triazolyl or pyrazolyl derivative. The compound represented by the formula (XLVII) is commercially available. The compound of formula (VII) can be prepared by a method analogous to that described in Scheme 11.

  Further details regarding the preparation of compounds of formula (I) can be found in the examples below.

  The compounds of the invention may be prepared alone or may be prepared as a compound library comprising at least 2, for example 5 to 1,000 compounds, for example 10 to 100 compounds. Libraries of compounds of the invention can be prepared by techniques known to those skilled in the art, using either liquid phase or solid phase chemistry, by a combinatorial “split and mix” approach, or by multiple parallel synthesis. Thus, according to a further aspect, there is provided a compound library comprising at least two compounds of the invention.

  The compounds of the present invention potentiate AMPA receptors. Compounds that potentiate AMPA receptors may be useful in the treatment of diseases and conditions mediated by potentiation of glutamate receptors.

  Thus, the present invention provides a compound of formula (I) or a salt or solvate thereof for use as a medicament as described in the first aspect of the present invention. As described above, the compound represented by the formula (I) is 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl. ] Phenyl] -1,2,3-thiadiazole-5-carboxamide and its salts.

  In one embodiment, the compound of formula (I) is selected from the group consisting of formulas (Ia), (Ib), (Ic), (Id), (Ie) and (If) as defined above It is a compound. As mentioned above, the compound of formula (Ia) is 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl. ] Phenyl] -1,2,3-thiadiazole-5-carboxamide and its salts.

［式中、Ｒ’およびＲ’’は、それらが結合している窒素原子と一緒になって、ピロリジニルまたはモルホリニルを形成する］
で示される化合物またはその塩もしくは溶媒和物を提供する。 In one embodiment, the formula (Ig) for use in medicine:

[Wherein R ′ and R ″ together with the nitrogen atom to which they are attached form pyrrolidinyl or morpholinyl]
Or a salt or solvate thereof.

［式中、Ｒ^１はＮＲ^２Ｒ^３基であり、ここに、Ｒ^２およびＲ^３は、それらが結合している窒素と一緒になって、５員の非芳香族ヘテロサイクリック環を形成し、これらは、ハロ、Ｃ_１−４アルキル、ハロＣ_１−４アルキル、およびケトから選択される１個またはそれ以上の基により置換されていてもよい］
で示される化合物またはその塩もしくは溶媒和物を提供する。 The present invention also provides a compound of formula (Ih):

[Wherein R ¹ is an NR ² R ³ group, where R ² and R ³ together with the nitrogen to which they are attached form a 5-membered non-aromatic heterocyclic ring. And these may be substituted by one or more groups selected from halo, C _1-4 alkyl, halo C _1-4 alkyl, and keto]
Or a salt or solvate thereof.

In one embodiment, R ² and R ³ together with the nitrogen atom to which they are attached form a pyrrolidinyl ring, from halo, C _1-4 alkyl, halo C _1-4 alkyl and keto It may be substituted by one or more selected groups.

  The present invention also provides a salt or solvate of the compound represented by the formula (Ih) as defined above for use in medicine.

  The invention also provides a pharmaceutical composition comprising a compound of formula (I) or a salt or solvate thereof and at least one carrier, diluent or excipient as described in the first aspect of the invention I will provide a. As described above, the compound represented by the formula (I) is 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl. ] Phenyl] -1,2,3-thiadiazole-5-carboxamide and its salts are excluded.

  In one embodiment, the compound of formula (I) is represented by formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig) and (Ih). Selected from the group consisting of: As mentioned above, the compound of formula (Ia) is 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl. ] Phenyl] -1,2,3-thiadiazole-5-carboxamide and its salts are excluded.

［式中：
ｑは０または１であり；
ｎは０、１または２であり；
ＸはＣＲ^６Ｒ^７であり、Ｒ^６およびＲ^７は、各々独立して、水素、メチルおよびフルオロからなる群から選択される：ただし、Ｒ^６およびＲ^７は、両方同時にメチルではない；あるいは、ｎが１である場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、水素、Ｃ_２−４アルケニルおよびＣ_１−４アルキルからなる群から選択され；
ｍは０または１であり；
ａ）ｎが０であり、ｍが１である場合、Ｒ^１は、（ｉ）Ｃ_１−４アルキル、（ｉｉ）メチルにより置換されていてもよいＣ−結合５員の芳香族ヘテロサイクリック基、（ｉｉｉ）ＮＨＲ^２および（ｉｖ）ＮＲ^２’Ｒ^３からなる群から選択され、ここに：
Ｒ^２は、Ｃ_１−６直鎖アルキル、Ｃ_４−６分枝鎖アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚは、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；ここに、ＹがＣＯである場合、Ｒ^２は（ＣＨ_２）_２ピロリジニル以外であり；
Ｒ^２’は、メチルおよびエチルからなる群から選択され；
Ｒ^３は、Ｃ_１−６アルキルおよび−（ＣＨ_２）_ｐＺ（ここに、ｐは１、２または３である）からなる群から選択され；
Ｚ’は、ヒドロキシ、メトキシ、ＮＨＭｅ、フェニルまたは５もしくは６員の非芳香族または芳香族ヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；あるいは
Ｒ^２’およびＲ^３は、それらが結合している窒素原子と一緒になって：
（ｉ）４または５員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、独立して、水素およびＣ_１−４アルキルからなる群から選択される）、ハロＣ_１−４アルキル、およびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；または
（ｉｉ）６員の非芳香族ヘテロサイクリック基（該環は、ハロ、ヒドロキシ、ＮＲ^１３Ｒ^１４（ここに、Ｒ^１３およびＲ^１４は、水素およびＣ_１−４アルキルからなる群から独立して選択される）、Ｃ_２−４アルキル、ハロＣ_１−４アルキルおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
を形成し；
ｂ）ｎおよびｍが、両方同時に０である場合、Ｒ^１は：
Ｃ_１−６アルコキシ；
炭素原子を介して結合する、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよい単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック基；
Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトからなる群から独立して選択される１、２または３個の基により置換されていてもよいＮ−結合ピロリジニル；および
Ｃ_１−４アルキルにより置換されていてもよい、オキサゾリルまたはイミダゾリル；
からなる群から選択され；
ｃ）ｎが１または２であり、ｍが１である場合、Ｒ^１は、Ｃ_１−４アルキル、ベンジル、シクロプロピル、チエニルおよびＮＲ^９Ｒ^１０からなる群から選択され、ここに：
Ｒ^９は、水素およびＣ_１−４アルキルからなる群から選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）からなる群から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルからなる群から独立して選択される１、２または３個の基により置換されていてもよく；または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック基または６員の非芳香族ヘテロサイクリック基を形成し、これらの環はいずれも、Ｃ_１−４アルキル、ハロ、フェニルおよび（非芳香環の場合）ケトからなる群から独立して選択される１、２または３個の基により置換されていてもよく；
ｄ）ｎが１または２であり、ｍが０である場合、Ｒ^１は、シアノ、ヒドロキシ、ＮＨ_２、Ｃ−結合５員の芳香族ヘテロサイクリック基（Ｃ_１−６アルキルおよびＣ_３−６シクロアルキル、およびＮＲ^１１Ｒ^１２からなる群から独立して選択される１、２または３個の基により置換されていてもよい）からなる群から選択され、ここに：
Ｒ^１１は水素であり、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか；またはＲ^１１は、Ｃ_１−４アルキルおよびＣ_２−４アルケニルからなる群から選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキル、ＳＯ_２Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、Ｃ（Ｏ）フェニルおよびＣ（Ｏ）Ｃ_２−４アルケニルからなる群から選択されるか、または
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって：
（ｉ）５員の芳香族ヘテロサイクリック基（ここに、Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシ、Ｃ_３−６シクロアルキルおよびＣ_１−４アルコキシからなる群から独立して選択される１または２個の基により置換されていてもよい）；
（ｉｉ）フェニルにより置換されているイミダゾリル；
（ｉｉｉ）５員の非芳香族ヘテロサイクリック基（ここに、ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；および
（ｉｖ）６員の非芳香族ヘテロサイクリック基（ここに、ケト、ヒドロキシおよびＣ_１−４アルコキシからなる群から独立して選択される１、２または３個の基により置換されていてもよい）；
からなる群から選択される基を形成する］
で示される化合物またはその塩もしくは溶媒和物を提供する。 The present invention also has formula (Ii) for use in the treatment of diseases and conditions mediated by glutamate receptors:

[Where:
q is 0 or 1;
n is 0, 1 or 2;
X is CR ⁶ R ⁷ and R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are not both methyl at the same time; or , When n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) a C-bonded 5-membered aromatic heterocyclic optionally substituted by methyl A group selected from the group consisting of (iii) NHR ² and (iv) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl; or R ^{2 '} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6 A membered non-aromatic heterocyclic group, wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl _{), C 2-4} alkyl, optionally substituted by one, two or three groups independently selected from the group consisting of halo _{C 1-4} alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2 and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² is a group consisting of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, Selected from the group consisting of C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are the nitrogen atom to which they are attached. With:
(I) a 5-membered aromatic heterocyclic group (wherein independent of the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups selected as above);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) And (iv) a 6-membered non-aromatic heterocyclic group (wherein substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); May be);
Forming a group selected from the group consisting of]
Or a salt or solvate thereof.

［式中：
ｑは、０または１であり；
ｎは、０、１、または２であり；
ＸはＣＲ^６Ｒ^７であり、ここにＲ^６およびＲ^７は、各々独立して、Ｈ、ＭｅおよびＦから選択される：ただし、Ｒ^６およびＲ^７は、両方同時にＭｅではない；あるいは、ｎが１である場合、Ｒ^６およびＲ^７は、それらが結合している炭素原子と一緒になって、３員の炭素環を形成し；
Ｙは、ＣＯ、ＮＲ^８ＣＯ、ＳＯ、ＳＯ_２およびＮＲ^８ＳＯ_２からなる群から選択され；
Ｒ^８は、ＨおよびＣ_１−４アルキルから選択され；
ｍは、０または１であり；
および
ａ）ｎが０であり、ｍが１である場合：
Ｒ^１は、Ｃ_１−４アルキル、およびＮＲ^２Ｒ^３からなる群から選択され、ここに
Ｒ^２はＣＨ_３であり、Ｒ^３は、Ｃ_１−６直鎖アルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは、１、２または３である）から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロ、Ｃ_１−４アルキルおよびハロＣ_１−４アルキルから選択される１個またはそれ以上の基により置換されていてもよく；または
Ｒ^２およびＲ^３は、それらが結合している窒素原子と一緒になって、５員の非芳香族ヘテロサイクリック環を形成し、該環は、ハロ、Ｃ_１−４アルキル、ハロＣ_１−４アルキル、およびケトから選択される１個またはそれ以上により置換されていてもよく；
ｂ）ｎおよびｍが両方とも同時に０の場合；
Ｒ^１は、Ｃ_１−４アルキル、Ｃ（Ｏ）Ｃ_１−４アルキル、ハロＣ_１−４アルキル、ハロおよびケトから選択される１個またはそれ以上の基により置換されていてもよい、炭素原子を介して結合する、単環式飽和または部分的に不飽和の５または６員のヘテロサイクリック環であり；
ｃ）ｎが１または２であり、ｍが１である場合
Ｒ^１は、Ｃ_１−４アルキルおよびＮＲ^９Ｒ^１０からなる群から選択され、ここに
Ｒ^９は、水素およびＣ_１−４アルキルから選択され、Ｒ^１０は、Ｃ_１−６直鎖アルキル、Ｃ_３−６シクロアルキル、Ｃ（Ｏ）Ｃ_１−４アルキルおよび−（ＣＨ_２）_ｐＺ（式中、ｐは１、２または３である）から選択され；
Ｚは、フェニルまたは５もしくは６員のヘテロサイクリック基であり、該フェニルまたはヘテロサイクリック基は、ハロおよびＣ_１−４アルキルから選択される１個またはそれ以上の基により置換されていてもよく；または
Ｒ^９およびＲ^１０は、それらが結合している窒素原子と一緒になって、５員の芳香族または非芳香族ヘテロサイクリック環または６員の非芳香族ヘテロサイクリック環を形成し、これらはいずれも、Ｎ、ＯまたはＳから選択される１個またはそれ以上のさらなるヘテロ原子を含有していてもよく、Ｃ_１−４アルキル、ハロ、および（非芳香環の場合）ケトから選択される１個またはそれ以上の基により置換されていてもよく；
ｄ）ｎが１または２であり、ｍが０である場合
Ｒ^１は、シアノ、ＯＨ、ＮＨ_２およびＮＲ^１１Ｒ^１２からなる群から選択され、ここに
Ｒ^１１は、ＨおよびＣ_１−４アルキルから選択され、Ｒ^１２は、ＳＯ_２Ｃ_１−４アルキルおよびＣ（Ｏ）Ｃ_１−４アルキルから選択されるか；あるいは
Ｒ^１１およびＲ^１２は、それらが結合している窒素原子と一緒になって、５員の芳香族ヘテロサイクリック環、５員の非芳香族ヘテロサイクリック環および６員の非芳香族ヘテロサイクリック環から選択される基を形成し、これらはいずれも、Ｎ、ＯまたはＳから選択される１個またはそれ以上のさらなるヘテロ原子を含有していてもよく、５員の芳香族ヘテロサイクリック環は、Ｃ_１−４アルキル、ハロ、ハロＣ_１−４アルキル、ヒドロキシおよびＣ_１−４アルコキシから選択される１個またはそれ以上の基により置換されていてもよく；５員の非芳香族ヘテロサイクリック環は、ケト、ヒドロキシおよびＣ_１−４アルコキシから選択される１個またはそれ以上の基により置換されていてもよく；６員の非芳香族ヘテロサイクリック環は、ケト、ヒドロキシおよびＣ_１−４アルコキシから選択される１個またはそれ以上の基により置換されていてもよい］
で示される化合物またはその塩もしくは溶媒和物を提供する。 The present invention also provides formula (J) for use as a medicament:

[Where:
q is 0 or 1;
n is 0, 1, or 2;
X is CR ⁶ R ⁷ where R ⁶ and R ⁷ are each independently selected from H, Me and F: provided that R ⁶ and R ⁷ are not both Me at the same time; when n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from H and C _1-4 alkyl;
m is 0 or 1;
And a) when n is 0 and m is 1:
R ¹ is selected from the group consisting of C _1-4 alkyl, and NR ² R ³ , wherein R ² is CH ₃ , R ³ is C _1-6 linear alkyl, C (O) C _{1 -4} alkyl and - _{(CH 2) (wherein,} p is 1, 2 or 3) p Z is selected from;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is one or more selected from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by a group; or R ² and R ³ together with the nitrogen atom to which they are attached form a 5-membered non-aromatic heterocyclic ring, which is a halo Optionally substituted by one or more selected from: C _1-4 alkyl, halo C _1-4 alkyl, and keto;
b) when n and m are both 0 at the same time;
R ¹ is a carbon, optionally substituted by one or more groups selected from C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic ring bonded through an atom;
c) when n is 1 or 2 and m is 1 R ¹ is selected from the group consisting of C _1-4 alkyl and NR ⁹ R ¹⁰ , wherein R ⁹ is hydrogen and C _1-4 alkyl R ¹⁰ is C _1-6 straight chain alkyl, C _3-6 cycloalkyl, C (O) C _1-4 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3) is selected from;
Z is phenyl or a 5 or 6 membered heterocyclic group, which phenyl or heterocyclic group may be substituted by one or more groups selected from halo and C _1-4 alkyl Well; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached form a 5-membered aromatic or non-aromatic heterocyclic ring or a 6-membered non-aromatic heterocyclic ring Each of which may contain one or more additional heteroatoms selected from N, O or S, C _1-4 alkyl, halo, and (if non-aromatic ring) keto Optionally substituted by one or more groups selected from:
d) when n is 1 or 2 and m is 0 R ¹ is selected from the group consisting of cyano, OH, NH ₂ and NR ¹¹ R ¹² , wherein R ¹¹ is H and C _1-4 Selected from alkyl and R ¹² is selected from SO ₂ C _1-4 alkyl and C (O) C _1-4 alkyl; or R ¹¹ and R ¹² together with the nitrogen atom to which they are attached. To form a group selected from a 5-membered aromatic heterocyclic ring, a 5-membered non-aromatic heterocyclic ring and a 6-membered non-aromatic heterocyclic ring, both of which are N , O or S, which may contain one or more further heteroatoms selected from C _1-4 alkyl, halo, halo C _1-4 alkyl , Hydroxy And optionally substituted by one or more groups selected from C _1-4 alkoxy; the 5-membered non-aromatic heterocyclic ring is selected from keto, hydroxy and C _1-4 alkoxy Optionally substituted by one or more groups; the 6-membered non-aromatic heterocyclic ring is substituted by one or more groups selected from keto, hydroxy and C _1-4 alkoxy. It may be]
Or a salt or solvate thereof.

  Descriptions of specific examples of compounds of formulas (I), (A), (Ia), (Ib), (Ic), (Id), (Ie), (If) are described with respect to each other and to formula (Ig) The same applies to the compounds of formula (Ih) and formula (Ii).

For diseases and conditions mediated by glutamate receptors for use as a medicament as described herein, or in a composition as described herein, or as described herein Examples of compounds for use in therapy include:
N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-pyrrolidinylcarbonyl) phenyl ] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N- (phenylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamido N-ethyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl Benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl- -(2-Phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N, N-dimethyl-4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone 1 -[4- (Methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5, 6,7-Tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamido N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} a Cetamide N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-Phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1-{[4- (1 -Pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1-methyl-2-oxo-2- (1) -Pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3-oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pyrrolidinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H Indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetra Dro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N- Cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-thienylmethyl)- 2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl ) Acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl-N- ( {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-ethyl-N-({4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H-imidazol-1-yl) propyl] -N-methyl-4- [3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (2-thienyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1H-1,2,4-triazol-1-yl) ethyl] -4- [3- (trifluoromethyl)- , 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1,3-thiazol-2-ylmethyl) -4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1-methyl-1H-pyrrol-2-yl) ethyl] -4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] benzamide N- (2-furanylmethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-[(4-fluorophenyl) methyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4 -(4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4, 5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- {4- [1-fluoro-2-oxo-2- (1-pyrrolidi) L) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1,1-difluoro-2-oxo-2- (1-pyrrolidinyl) ) Ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- (4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] methyl} phenyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-y ] Phenyl} methyl) -1-pyrrolidinecarboxamide 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- (1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide N-methyl-N- (1- {4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide 1- [4- (1-acetyl-2-pyrrolidinyl) phenyl] -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydr B-1H-indazol-1-yl] phenyl} ethyl) -2-pyrrolidinone 1- {4-[(1,1-dioxide-2-isothiazolidinyl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 2-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) butanamide N-({4 -[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-thiophenecarboxamide N-({4- [ -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamido N-methyl-2-phenyl-N-({4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide N- (2-hydroxyethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] benzamido N-methyl-N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydride -1H-indazol-1-yl] benzamide N-methyl-N- [2- (methylamino) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole -1-yl] benzamido 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinol N-methyl -1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinamine 1- [4- (1 -Azetidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1-({4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-azetidinol (3,3-difluorocyclobutyl) {4- [3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazol-1-yl] phenyl} methanone 1- [4- (1H-imidazol-1-yl) phenyl] -3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N- (1-methylethenyl) -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ) -2-propenamide N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2 -Propenamide 1- {4-[(3-methyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole 1- {4-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazole N-ethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1-methyl Ethyl)- -[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-piperidinylcarbonyl) phenyl] -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole N, N-diethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Benzamide N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- {4- [2-oxo-2- (2) -Phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (to (Rifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide 1- [4- (1,3-oxazol-5-yl) phenyl] -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (propyloxy) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazole 1- [4- (1-methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propanesulfonamide N-({4- [3- Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide 1- [4- (1-pyrrolidinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazole N- (2-methylpropyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (4-morpholinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Dandazole N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- [2- (1-Pyrrolidinyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- (tetrahydro-2-furanylmethyl)- 4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (1H-imidazol-1-ylmethyl) phenyl] -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,4-triazol-1-ylme Til) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-pyrazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,3-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazole 1- [4- (2H-1,2,3-triazol-2-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H Indazole 1- {4-[(4-methyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Zole 1- {4-[(3,5-dimethyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 3- (Trifluoromethyl) -1- (4-{[3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 3- ( Trifluoromethyl) -1- (4-{[5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4 -{[5-Methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Sol 1- (4-{[3-methyl-5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole 1- {4-[(2-methyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1 -(4-{[2- (1-methylethyl) -1H-imidazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1 -{4-[(4-Phenyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [(4-Bromo-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-1H-imidazole-2- Yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone N-methyl-N- {4- [3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide and its salts and solvates.

It will be clear that the invention includes the following further aspects. Hereinafter, the term “the compound of the present invention” means the compound represented by the formula (Ii) described in the embodiment of the present invention, a salt thereof, and a solvate thereof (excluding intermediate compounds of chemical synthesis). The embodiment described with respect to the first aspect applies equally to each of these further aspects:
i) use of a compound of formula (Ii) or a salt or solvate thereof in the manufacture of a medicament for treating a disease or condition mediated by reduced or unbalanced glutamate receptor function in a mammal;
ii) a compound of formula (Ii) or a salt or solvate thereof for use in treating a disease or condition mediated by reduced or imbalanced glutamate receptor function in a mammal;
iii) a method for treating a disease or condition mediated by reduced or unbalanced glutamate receptor function in a mammal, comprising administering an effective amount of a compound of formula (Ii) or a salt or solvate thereof A method comprising:
iv) a combination product of a compound of formula (Ii) or a salt or solvate thereof and an antipsychotic;
v) A pharmaceutical composition comprising a combination product as defined in iv) above and at least one carrier, diluent or excipient;
vi) use of a combination product as defined in iv) above in the manufacture of a medicament for treating a disease or condition mediated by reduced or imbalanced glutamate receptor function in a mammal;
vii) a combination product as defined in iv) above for use in treating a disease or condition mediated by reduced or imbalanced glutamate receptor function in a mammal;
viii) a combined product as defined in iv) above for use as a medicament;
ix) A method of treating a disease or condition mediated by reduced or imbalanced glutamate receptor function in a mammal, comprising administering an effective amount of a combination product as defined in iv) above.

  In the case of aspects ii), iii), iv), vii), viii), ix) and xi), the relevant diseases or symptoms are: psychosis and mental disorders (schizophrenia, schizophrenic emotional disorder, schizophrenia) Type disease, short-term psychosis, childhood-onset schizophrenia, “schizophrenia spectrum” disorders, such as schizophrenic personality disorder, acute psychosis, alcoholic psychosis, drug-induced psychosis, autism, delirium, mania ( (Including acute epilepsy), manic-depressive psychosis, hallucinations, intrinsic psychosis, organic psychosis, paranoia and delusional disorders, postpartum psychosis, and psychosis associated with neurodegenerative diseases such as Alzheimer's disease); Disorders (including alcohol-related disorders and nicotine-related disorders); cognitive impairment (eg, cognitive impairment including attention, adaptation, memory (ie, memory impairment, Treatment of forgetfulness, amnestic disorders and memory impairment due to aging) and speech impairment, as well as dementia or other dementia associated with stroke, Alzheimer's disease, AIDS, and cognitive decline such as delirium or depression Obtain other acute or subacute conditions (pseudo-dementia conditions), trauma, aging, stroke, neurodegeneration, drug-induced conditions, including cognitive impairment as a result of neurotoxic agents), mild cognitive impairment, aging Cognitive impairment due to autism, cognitive impairment related to autism, Down syndrome, cognitive decline related to psychosis, cognitive impairment after electroshock therapy; anxiety disorder (generalized anxiety disorder, social anxiety disorder, excitement, tension, psychosis Including social or emotional withdrawal, panic disorder, and obsessive compulsive disorder); neurodegenerative diseases (eg, Alzheimer's disease, amyotrophic lateral sclerosis, motor nuisance) Ron's disease and other movement disorders such as Parkinson's disease (slowly increasing disability in intentional movements, tremors, slow movements, hyperactivity (moderate and severe), ataxia, stiffness, balance and coordination disorders , And reduction of motor deficits and / or disability, including postural disorders), dementia in Parkinson's disease, dementia in Huntington's disease, neuroleptic-induced parkinsonism and late-onset dyskinesia, stroke, Neurodegeneration after cardiac arrest, pulmonary bypass, traumatic brain injury, spinal cord injury, and demyelinating diseases such as multiple sclerosis and amyotrophic lateral sclerosis; depression (the term is bipolar ( Gonorrhea) Depression (including type I and type II), unipolar depression, or psychotic features, catatony features, melancholic features, atypical features (eg Single, or recurrent major depressive episodes with or without postpartum onset, seasonal affective disorder and mood modulation, depression-related anxiety, psychotic depression, and limited Not including depression disorders resulting from common medical conditions including myocardial infarction, diabetes, miscarriage or abortion); post-traumatic stress syndrome; attention deficit disorder; attention deficit hyperactivity disorder; drug induced ( Phencyclidine, ketamine and other dissociative anesthetics, amphetamine and other psychostimulants and cocaine) disorders; Huntington's disease; tardive dyskinesia; dystonia; myoclonus; spasticity; obesity; As well as some types of epilepsy.

  In the present invention, the terms describing the indications used herein are the diagnostic and statistical manuals for mental disorders and the statistical manual published by the American Psychiatric Association. of Mental Disorders 4th edition (DSM-IV) and / or the International Classification of Diseases 10th edition (ICD-10). Various subtypes of disorders listed herein are contemplated as part of the present invention. The numbers in parentheses after the diseases listed below indicate the classification code in DSM-IV.

In the present invention, the term “mental disorder”
Integration including subtype delusion type (295.30), disassembly type (295.10), tension type (295.20), undifferentiated type (295.90) and remnant type (295.60) Schizophrenia; Schizophrenia-like Disorder (295.40); Schizophrenic Emotional Disorders (295.70) including Subtype Bipolar and Depressive Types; Subtype Erotonic, Gradiose Delusional disorders (297.1), including (Jealous) type, Persecutive type, Somatic type, Mixed type and Unspecified type; Simple mental disorder (298.8); Common mental disorders (297.3); due to general health conditions, including subtypes with delusions and subtypes with hallucinations Psychiatric disorders; including substance-induced psychiatric disorders including subtypes with delusions (293.81) and hallucinations (293.82); and unspecified psychiatric disorders (298.9).

  The compounds of the present invention may also be useful in the treatment of the following disorders:

Depressive and mood disorders including major depressive episodes, mania episodes, mixed episodes and hypomania episodes; depressive disorders including major depressive disorder, dysthymic disorder (300.4), unspecified depressive disorder (311) Type I bipolar disorder, type II bipolar disorder (recurrent major depression episode with hypomania) (296.89), mood circulatory disorder (301.13) and unspecified bipolar disorder (296.80) Other moods including mood disorders due to general health conditions (293.83), including subtypes with depressive features, major depression-like episodes, manic features and mixed features Disorders, substance-induced mood disorders (including subtypes with depression characteristics, mania characteristics and mixed characteristics) and unspecified mood disorders (296.90):

Panic attack; Panic disorder including panic disorder without agoraphobia (300.01) and panic disorder with agoraphobia (300.21); agoraphobia; agoraphobia without history of panic disorder (300.22), animal type, natural environment type, Blood-Injection-Injury type, situation type and other types of subtypes (300.29, previous single fear) Disease (Simple Phobia)), social phobia (social anxiety disorder, 300.23), obsessive-compulsive disorder (300.3), post-traumatic stress disorder (309.81), acute stress disorder (308.3), generalized anxiety Disorder (300.02), anxiety disorder due to general health condition (293.84), substance-induced anxiety disorder, separation anxiety disorder (309.21) Anxiety disorders, including adjustment disorder (309.24) and unspecified anxiety disorders with anxiety (300.00):

Substance use disorders such as substance dependence, substance craving and substance abuse; substance poisoning, substance withdrawal, substance induced delirium, substance induced persistent dementia, substance induced persistent amnesia disorder, substance induced mental disorder, substance induced Substance-induced disorders such as mood disorders, substance-induced anxiety disorders, substance-induced sexual dysfunction, substance-induced sleep disorders and hallucinogen persistent sensory disturbances (flashback); alcohol dependence (303.90), alcohol abuse (305.00), alcoholism (303.00), alcohol withdrawal (291.81), alcoholism delirium, alcohol withdrawal delirium, alcohol-induced persistent dementia, alcohol-induced persistent amnesia, alcohol-induced mentality Disorder, alcohol-induced mood disorder, alcohol-induced anxiety disorder, alcohol-induced sexual dysfunction, alcohol induction Alcohol-related disorders such as sleep disorders and unspecified alcohol-related disorders (291.9); amphetamine dependence (304.40), amphetamine abuse (305.70), amphetamine addiction (292.89), amphetamine withdrawal (292.0) ), Amphetamine intoxication delirium, amphetamine-induced psychiatric disorder, amphetamine-induced mood disorder, amphetamine-induced anxiety disorder, amphetamine-induced sexual dysfunction, amphetamine-induced sleep disorder and unspecified amphetamine-related disorders (292.9) Caffeine-related disorders such as caffeine addiction (305.90), caffeine-induced anxiety disorder, caffeine-induced sleep disorder and unspecified caffeine-related disorders (292.9) Obstacle; cannabis (304.30), cannabis abuse (305.20), cannabis poisoning (292.89), cannabis poisoning delirium, cannabis-induced psychiatric disorders, cannabis-induced anxiety disorder and unspecified cannabis-related disorders (292.9) Cannabis-related disorders such as: cocaine dependence (304.20), cocaine abuse (305.60), cocaine addiction (292.89), cocaine withdrawal (292.0), cocaine addiction delirium, cocaine-induced psychiatric disorder, cocaine induction Cocaine-related disorders such as cognitive mood disorders, cocaine-induced anxiety disorder, cocaine-induced sexual dysfunction, cocaine-induced sleep disorder and unspecified cocaine-related disorders (292.9); hallucinogen dependence (304.50), hallucinations Abuse of drugs (305.30), hallucinogen poisoning (292.89), hallucinogen persistent sensory disturbance (flashback) (292.89), hallucinogen poisoning Hallucinogen-related disorders such as delirium, hallucinogen-induced mental disorders, hallucinogen-induced mood disorders, hallucinogen-induced anxiety disorders and unspecified hallucinogen-related disorders (292.9); inhalant dependent (304.60) ), Inhalant abuse (305.90), inhalant poisoning (292.89), inhalant delirium delirium, inhalant-induced persistent dementia, inhalant-induced mental disorder, inhalant-induced mood disorder, inhaler Inhalant-related disorders such as induced anxiety disorder and unspecified inhalant-related disorders (292.9); nicotine dependence (305.1), nicotine withdrawal (292.0) and unspecified nicotine-related disorders (292.9) Nicotine-related disorders such as: opioid dependence (304.00), opioid abuse (305.50), opioid addiction (292.89), opioid withdrawal (292.0), opioid addiction delirium, opioid Opioid-related disorders such as induced psychiatric disorders, opioid-induced mood disorders, opioid-induced sexual dysfunction, opioid-induced sleep disorders and unspecified opioid-related disorders (292.9); phencyclidine-dependent (304.60) , Phencyclidine abuse (305.90), phencyclidine addiction (292.89), phencyclidine addiction delirium, phencyclidine-induced mental disorder, phencyclidine-induced mood disorder, phencyclidine-induced anxiety disorder And phencyclidine (or phencyclidine-like) -related disorders such as unspecified phencyclidine-related disorders (292.9); sedative, hypnotic or anxiolytic-dependent (304.10), sedatives, hypnotics Or anxiolytic abuse (305.40), sedative, hypnotic or anxiolytic addiction (292.8) ), Sedative, hypnotic or anxiolytic release (292.0), sedative, hypnotic or anxiolytic addiction delirium, sedative, hypnotic or anxiolytic release delirium, sedative, hypnotic or anxiolytic Persistent dementia, sedative, hypnotic or anxiolytic, persistent amnestic disorder, sedative, hypnotic or anxiolytic-induced mental disorder, sedative, hypnotic or anxiolytic-induced mood disorder, sedative , Hypnotic or anxiolytic-induced anxiety disorder, sedative, hypnotic or anxiolytic-induced sexual dysfunction, sedative, hypnotic or anxiolytic-induced sleep disorder and unspecified sedative, hypnotic Or sedatives such as anxiolytic-related disorders (292.9), hypnotic or anxiolytic-related disorders; multi-substance-related disorders such as multi-substance dependence (304.80); and anabolic steroids, nitrate inhalants and Substance-related disorders, including other (or unknown) substance-related disorders such as nitrous oxide:

Primary sleep disorders such as dyssomnia such as primary insomnia (307.42), primary hypersomnia (307.44), narcolepsy (347), respiratory related sleep disorder (780.59), Circadian rhythm sleep disorders (307.45) and unspecified sleep disorders (307.47); primary sleep disorders such as abnormal sleep behaviors such as nightmare disorder (307.47), sleep fear disorder (307.46) ), Gait walking disorder (307.46) and unspecified sleep abnormal behavior (307.47); sleep disorder associated with another mental disorder, eg, insomnia associated with another mental disorder (307.42) Hypersomnia associated with other mental disorders (307.44); sleep disorders due to general health conditions, particularly neurological disorders, neuropathic pain, restless leg syndrome, heart and Sleep disorders associated with diseases such as lung disease; and substance-induced sleep disorders, including insomnia, hypersomnia, sleep abnormal behavior and mixed subtypes; sleep apnea and jet lag syndrome Sleeping disorder:

Autistic disorder (299.00), Asperger's disorder (299.80), Rett disorder (299.80), childhood disintegrative disorder (299.10) and unspecified pervasive disorder (299.80, atypical self Disorders in the area of autism including (including autism):

Mixed attention deficit / hyperactivity disorder (314.01), inattention attention deficit / hyperactivity disorder (314.00), hyperactivity-impulsive attention deficit / hyperactivity disorder (314.01) ) And unspecified attention deficit / hyperactivity disorder (314.9) subtypes; attention deficit / hyperactivity disorder; hyperactivity disorder; disruptive behavior disorder, eg early childhood onset (321.81) Behavioral disorders, including adolescent-onset (312.82) and unspecified (312.89) subtypes, rebellious behavioral disorders (313.81) and unspecified destructive behavioral disorders; and Tourette's disorder Tic disorders such as (307.23):

  Delusional personality disorder (301.0), schizophrenic personality disorder (301.20), schizophrenic personality disorder (301, 22), nonsocial personality disorder (301.7), borderline personality disorder ( 301,83), acting personality disorder (301.50), self-loving personality disorder (301,81), avoidable personality disorder (301.82), dependent personality disorder (301.6), obsessive-compulsive personality disorder (301.4) and unspecified personality disorder (301.9) personality disorders, including subtypes:

Enhanced cognition, including treatment of cognitive impairment in other diseases such as schizophrenia, bipolar disorder, depression, cognitive impairment, other mental disorders and cognitive disorders such as Alzheimer's disease:

Sexual desire disorders such as hyposexual desire disorder (302.71) and sexual aversion disorder (302.79); Sexual stimulation disorders such as female sexual stimulation disorder (302.72) and male erectile dysfunction ( 302.72); organism disorders such as female organism disorder (302.73), male organism disorder (302.74) and premature ejaculation (302.75); sexual pain disorders such as sexual pain (302.76) And vaginal spasticity (306.51); unspecified sexual dysfunction (302.70); sexual perversion, eg, exposure (302.4), fetishism (302.81), friction lovers (302.89) ), Pedophilia (302.2), sexual masochism (302.83), sexual sadism (302.84), incongruity fetishism (302.3), sighting (30 .82) and unspecified sexual perversion (302.9); sexual self-identity disorders such as sexual self-identity disorder in children (302.6) and sexual self-identity disorder in adolescents or adults ( Sexual dysfunction, including unspecified sexual disorders (302.9).

  All of the various types and subtypes of disorders listed herein form part of the present invention.

  In the present invention, the term “cognitive impairment” means, for example, cognitive impairment including attention, adaptation, learning impairment, memory (ie, memory impairment, amnesia, amnesia, transient global amnesia syndrome and Memory impairment due to aging) and impaired language function; stroke, Alzheimer's disease, Huntington's disease, Pick's disease, AIDS-related or multiple infarct dementia, alcoholic dementia, hypothyroidism-related dementia, and cerebellar atrophy And cognitive impairment as a result of other dementia conditions such as dementia associated with other degenerative disorders such as amyotrophic lateral sclerosis; other acute or sub-acute that can cause cognitive decline such as delirium or depression Acute state (pseudo-dementia state), trauma, head trauma, age-related cognitive decline, stroke, neurodegeneration, drug-induced state, cognitive impairment as a result of neurotoxic agents, mild cognitive impairment, Cognitive impairment by age, cognitive impairment associated with autism, Down syndrome, cognitive decline associated with psychosis, and cognitive impairment after electroshock therapy; and Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesia Includes treatment of movement disorders.

In one embodiment, the present invention provides a compound of the present invention for use in the treatment of schizophrenia or cognitive impairment.
In one embodiment, the present invention provides the use of a compound of the present invention in the manufacture of a medicament for the treatment of schizophrenia or cognitive impairment.

  In one embodiment, the present invention provides a method of treating human schizophrenia, wherein a therapeutically effective amount of a compound of the present invention, alone or a pharmaceutically acceptable carrier, diluent or excipient. And a method comprising administering in combination.

  In one embodiment, the compounds used in the compositions, methods and uses of the present invention are 1- [4- (1-pyrrolidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6. , 7-tetrahydro-1H-indazole or a salt or solvate thereof, or 1- [4- (4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole or a salt or solvate thereof.

  In one embodiment, the present invention is a method of treating human schizophrenia, wherein the therapeutically effective amount of 1- [4- (1-pyrrolidinylcarbonyl) phenyl] -3- (trifluoro There is provided a method comprising administering methyl) -4,5,6,7-tetrahydro-1H-indazole or a salt thereof alone or in combination with a pharmaceutically acceptable carrier, diluent or excipient. In one embodiment, the method comprises combining the compound or salt thereof with other antipsychotic agents.

  In one embodiment, the present invention is a method for the treatment of human schizophrenia comprising a therapeutically effective amount of 1- [4- (4-morpholinylcarbonyl) phenyl] -3- (trifluoro There is provided a method comprising administering methyl) -4,5,6,7-tetrahydro-1H-indazole or a salt thereof alone or in combination with a pharmaceutically acceptable carrier, diluent or excipient. In one embodiment, the method includes combining the compound or salt thereof with other antipsychotic agents.

  In one embodiment, the present invention is a method for the treatment of human cognitive impairment, wherein a therapeutically effective amount of a compound of the present invention, alone or a pharmaceutically acceptable carrier, diluent or excipient. And a method comprising administering in combination.

  In one embodiment, the present invention is a method for the treatment of human cognitive impairment, comprising a therapeutically effective amount of 1- [4- (1-pyrrolidinylcarbonyl) phenyl] -3- (trifluoro There is provided a method comprising administering methyl) -4,5,6,7-tetrahydro-1H-indazole or a salt thereof alone or in combination with a pharmaceutically acceptable carrier, diluent or excipient.

  In one embodiment, the present invention is a method for the treatment of human cognitive impairment, comprising a therapeutically effective amount of 1- [4- (4-morpholinylcarbonyl) phenyl] -3- (trifluoro There is provided a method comprising administering methyl) -4,5,6,7-tetrahydro-1H-indazole or a salt thereof alone or in combination with a pharmaceutically acceptable carrier, diluent or excipient.

  In one embodiment, the present invention provides 1- [4- (1-pyrrolidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole or a salt thereof And a pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluent or excipient.

  In one embodiment, the present invention provides 1- [4- (4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole or a salt thereof And a pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluent or excipient.

  It is understood that the term “disease or condition mediated by a decrease or imbalance in mammalian glutamate receptor function” includes “a disease or condition caused by a decrease or imbalance in mammalian glutamate receptor function”. Will be done.

  The compounds of the present invention include the following agents for treating one or more psychiatric disorders: i) antipsychotics (olanzapine, risperidone, clozapine, zipradidone, talnetran, etc.); ii) extrapyramidal side effects such as , Anticholinergic drugs (benztropine, biperidene, procyclidine, trihexyphenidyl, etc.), antihistidine drugs (diphenhydramine), dopamine agonists (amantadine, etc.); iii) antidepressants; iv) anxiolytics; v) nootropic It may be used in combination with drugs such as cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine, etc.).

  The compounds of the present invention may be used in combination with antidepressants to treat depression and mood disorders.

  The compounds of the present invention may be used in combination with the following agents for treating one or more bipolar diseases: i) mood stabilizers; ii) antipsychotics; iii) antidepressants.

  The compounds of the present invention may be used in combination with the following agents for treating one or more anxiety disorders: i) anxiolytics; ii) antidepressants.

  The compounds of the present invention improve the one or more nicotine withdrawal and reduce nicotine craving: i) nicotine replacement therapy, eg sublingual prescription of nicotine β-cyclodextrin and nicotine patch; ii ) It may be used in combination with a nicotine addiction therapeutic, such as bupropion.

  The compounds of the present invention improve the one or more alcohol withdrawal and reduce alcohol craving: i) NMDA receptor antagonists such as acamprosate; ii) GABA receptor agonists such as Tetrabamate; iii) may be used in combination with opioid receptor antagonists such as naltrexone.

  The compounds of the present invention improve one or more opiate withdrawal and reduce opiate craving: i) opioid mu receptor agonist / opioid k receptor antagonist, eg buprenorphine; ii) opioid receptor Body antagonists such as naltrexone; iii) may be used in combination with vasodilator antihypertensive agents such as lofexidine.

  The compounds of the present invention include the following agents for treating one or more sleep disorders: i) benzodiazepines such as temazepam, lormetazepam, estazolam, triazolam; ii) non-benzodiazepine hypnotics such as zolpidem, zopiclone, zalepion Iii) barbituric acid hypnotics such as aprobarbital, butabarbital, pentobarbital, secobarbital, phenobarbital; iv) antidepressants; v) other hypnotic sedatives such as chloral hydrate, It may be used in combination with chlormethiazole.

  The compounds of the present invention include the following agents for treating one or more anorexia nerds: i) appetite stimulants such as cyproheptidine; ii) antidepressants; iii) antipsychotics; iv) zinc; v) It may be used in combination with premenstrual drugs such as pyridoxine and progesterone.

  The compounds of the present invention include the following agents for treating one or more bulimia: i) antidepressants; ii) opioid receptor antagonists; iii) antiemetics such as ondansetron; iv) testosterone reception Body antagonists such as flutamide; v) mood stabilizers; vi) zinc; vii) may be used in combination with premenstrual drugs.

  The compounds of the present invention include the following agents for treating one or more autism: i) antipsychotics; ii) antidepressants; iii) anxiolytics; iv) stimulants such as methylpheny May be used in combination with dating, amphetamine prescription, pemoline.

  The compounds of the present invention include the following agents for treating one or more attention deficit hyperactivity disorders: i) stimulants such as methylphenidate, amphetamine formulations, pemoline; ii) non-excitatory agents such as It may also be used in combination with norepinephrine reuptake inhibitors (such as atomoxetine), α2 adrenergic receptor agonists (such as clonidine), antidepressants, modafinil, cholinesterase inhibitors (galantamine and donepezil).

  The compounds of the present invention are used in combination with the following agents for treating one or more personality disorders: i) antipsychotics; ii) antidepressants; iii) mood stabilizers; iv) anxiolytics May be.

  The compounds of the present invention include the following agents for treating sexual dysfunction in one or more males: i) phosphodiesterase V inhibitors such as vardenafil, sildenafil; ii) dopamine agonist / dopamine transport inhibitors such as Iii) alpha adrenergic receptor antagonists such as phentolamine; iv) prostaglandin agonists such as alprostadil; v) testosterone agonists such as testosterone; vi) serotonin transport inhibitors such as serotonin re- Uptake inhibitors; v) noradrenaline transport inhibitors such as reboxetine; vii) 5-HT1A agonists such as firibanserin may be used in combination.

  The compounds of the present invention include the following agents for treating one or more female sexual dysfunctions: i) the same agent as defined in male sexual dysfunction, ii) an estrogen agonist such as estradiol They may be used in combination.

  Antipsychotics are typically antipsychotics (eg, chlorpromazine, thioridazine, mesoridazine, fluphenazine, perphenazine, flurozine, prochlorzine, prochlorzine, prochlorzine) Operadin (trifluoperazine), thiothixine, haloperidol, morindone and loxapine; and atypical antipsychotics (eg, clozapine, olanzaperine, olanzaperine, (Risperidon ), Including quetiapine (quetiapine), aripiprazole (Aripirazole), ziprasidone (ziprasidone), amisulpride (Amisulpride), ziprasidone (Ziprazidone) and talnetant (talnetant)).

  Antidepressants are serotonin reuptake inhibitors (eg, citalopram, escitalopram, fluoxetine, paroxetine and sertraline (sertraline) (eg, dual serotonin / noradrenaline inhibitors) , Venlafaxine, duloxetine and milnacipran); noradrenaline reuptake inhibitors (eg, reboxetine); tricyclic antidepressants (eg, amitriptyline, clomipramine, ), Imipramine, maprotiriline, nortrip Monoamine oxidase inhibitors (eg, isocarboxazide, moclobemide, phenelzine and tranylcypromine); and others (eg, bupropion, mianserin, mirtazapine, mirtazapine) Nefazodone and trazodone).

  Mood stabilizers include lithium, sodium valproate / valproic acid / divalproex, carbamazepine, lamotrigine, gabapentin, topiramate and tiagabin.

  Anti-anxiety drugs include benzodiazepines such as alprazolam and lorazepam.

  The compounds of the present invention may be administered in conventional dosage forms prepared according to conventional techniques well known in the art by combining the compounds of the present invention with standard pharmaceutical carriers or diluents. These techniques may include mixing, granulating and compressing or dissolving the ingredients as appropriate to obtain the desired formulation.

The pharmaceutical compositions of the invention can be formulated for administration to mammals, including humans.
The composition can be formulated for administration by any route. The compositions are formulated for oral, topical or parenteral administration and may be in the form of tablets, capsules, powders, granules, lozenges, creams or liquid preparations such as oral or sterile parenteral solutions or suspensions. .

  The topical formulations of the present invention may be provided, for example, as ointments, creams or lotions, ophthalmic ointments and eye drops or ear drops, impregnated dressings and aerosols, suitable conventional additives such as preservatives Solvents to aid drug penetration, and emollients in ointments and creams may be included.

  The formulations may also contain compatible conventional carriers, such as cream or ointment bases and ethanol or oleyl alcohol for lotions. Such carriers may be included at a rate of about 1% to about 98% of the formulation. More usually they constitute up to about 80% of the formulation.

  Tablets and capsules for oral administration may be in unit dosage form, with conventional excipients such as binders such as syrup, gum arabic, gelatin, sorbitol, tragacanth gum, or polyvinylpyrrolidone; For example, lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine; tablet lubricants such as magnesium stearate, talc, polyethylene glycol or silica; disintegrants such as potato starch; or acceptable wetting agents such as It may contain sodium lauryl sulfate. The tablets may be coated according to methods well known in normal pharmaceutical practice. Oral liquid formulations may be, for example, in the form of an aqueous or oily suspension, solution, emulsion, syrup or elixir, or provided as a dry product for reconstitution with water or other suitable vehicle prior to use. May be. Such liquid formulations include conventional additives such as suspending agents such as sorbitol, methylcellulose, glucose syrup, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel or hydrogenated edible oils and fats, emulsifiers such as lecithin, Sorbitan monooleate, or gum arabic; non-aqueous vehicles (which may include edible oils), such as almond oil, oily esters, such as glycerin, polyethylene glycol, or ethyl alcohol; preservatives, such as p-hydroxybenzoic acid It may contain methyl or propyl or sorbic acid and, if necessary, conventional flavors or colorants.

  Suppositories contain conventional suppository bases such as cocoa butter or other glycerides.

  For parenteral administration, fluid unit dosage forms are prepared using the compound and a sterile vehicle, preferably water. The compound can be suspended or dissolved in the vehicle, depending on the vehicle and concentration used. In preparing solutions, the compound can be dissolved in water for injection and then filter sterilized before filling into a suitable vial or ampoule and sealing.

  Agents such as local anesthetics, preservatives and buffering agents can also be dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling the vial and dehydrated under vacuum. The lyophilized powder may then be sealed in a vial and an attached vial of water for injection may be provided to restore the liquid prior to use. Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended instead of dissolved in the vehicle and cannot be sterile filtered. The compound can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle. Surfactants or wetting agents can also be included in the composition to facilitate uniform distribution of the compound.

  Depending on the method of administration, the composition may contain from 0.1% by weight, eg, 10-60% by weight of the active substance. When the composition includes dosage unit amounts, each unit amount may contain, for example, 0.1-20 mg of the active ingredient. For example, such unit amounts may contain 1-10 mg. The dosage used for adult treatment will depend on the route of administration and frequency, for example 2-50 mg per day, for example per day (although in some cases a dosage of 50 mg to 100 mg per day may be appropriate) Such a dosage, based on a 75 kg individual that may range from 5 to 20 mg, corresponds to 0.027 to 0.667 mg / kg per day. Suitably the dosage is 0.05 to 0.3 mg / kg per day.

  Optimum amounts and intervals between individual doses of the compounds of the present invention are determined by the nature and extent of the condition being treated, the dosage form, route and site, and the particular mammal being treated, such optimal conditions It will be appreciated by those skilled in the art that can be determined by routine techniques. It will also be apparent to those skilled in the art that the optimal treatment regimen, i.e., the number of administrations of the compound of the invention given on a given day or day, can be determined by one skilled in the art using the usual course of treatment decision testing. Let's go.

  It will be appreciated that "treatment" as used herein includes prevention as well as reduction of existing symptoms. In one embodiment, the mammal being treated is a human.

The invention is illustrated by the examples described below.
Starting materials were obtained from commercial products and used without further purification unless otherwise noted. Flash chromatography was performed using a prepacked Isolute Flash ^™ or Biotage ^™ silica gel column as the stationary phase and an analytical grade solvent as the eluent.

NMR spectra were performed using a Bruker ^™ DPX400 or Oxford Instruments ^™ 250 MHz instrument, unless otherwise stated, using a diluted solution of 298 K, defined frequency, CDCl ₃ . All NMR spectra used tetramethylsilane (TMS δ _H 0, δ _C 0) as an internal standard. All coupling constants are listed in hertz (Hz) and multiplicity is s (singlet), bs, (broad singlet), d (doublet), t (triplet), q (quartet), dd (doublet doublet) ), Dt (doublet triplet) and m (multiplet).

  Total ion current traces were obtained for electrospray cation and anionization methods (ES + / ES-) and atmospheric pressure chemical cation and anionization methods (AP + / AP-).

  All retention times were measured using LC / MS (liquid chromatography / mass spectrum). Where appropriate, purification using mass directed automatic purification (MDAP), which means purification by HPLC, refers to these retention times and fraction collection is initiated by detection of the programmed mass ions of the compound of interest.

  Unless otherwise specified, compounds having all chiral centers are racemic.

流速： ３ｍｌ／分
注入容量： ５ｕｌ
カラム温度： ３０℃
ＵＶ波長範囲： ２２０−３３０ｎｍ LC / MS conditions, Examples 1-35 and 45-113
Column : Waters Atlantis, 4.6 mm x 50 mm; stationary phase particle size is 3 um
Solvent system: A: Aqueous solvent = water + 0.05% formic acid; B: Organic solvent = acetonitrile + 0.05% formic acid
Method: The general method used is a 5 minute runtime.

Flow rate: 3ml / min
Injection volume: 5ul
Column temperature : 30 ° C
UV wavelength range : 220-330 nm

流速： １ｍｌ／分
注入容量： ２ｕｌフルループ注入
カラム温度： 常温
ＵＶ波長範囲： ２１０−３５０ｎｍ LC / MS conditions, Examples 36-44
Column: Waters Atlantis, 4.6 mm x 20 mm; stationary phase particle size is 3 um
Solvent system: A: Aqueous solvent = water + 0.1% formic acid; B: Organic solvent = acetonitrile + 0.1% formic acid
Method: The general method is a 5.5 minute runtime using the following gradient program.

Flow rate: 1 ml / min
Injection volume: 2ul full loop injection
Column temperature : normal temperature
UV wavelength range : 210-350nm

MDAP conditions, Examples 1-35 and 45-113
Column: Waters Atlantis, 19 mm x 100 mm (small scale) and 30 mm x 100 mm (large scale); stationary phase particle size = 5 um
Solvent system: A: aqueous solvent = water + 0.1% formic acid; B: organic solvent = acetonitrile + 0.1% formic acid. Make-up solvent = methanol: water 80:20. Needle cleaning solvent = methanol
Methods: Five methods are used depending on the analytical retention time of the target compound. These have a runtime of 13.5-min (including a 10-min ramp time followed by a 3.5 min column flush and re-equilibration step).
Large / Small 1.0-1.5 = 5-30% B
Large / Small 1.5-2.2 = 15-55% B
Large / Small 2.2-2.9 = 30-85% B
Large / small 2.9-3.6 = 50-99% B
Large / Small 3.6-5.0 = 80-99% B (6 minutes, then 7.5 minutes flash and re-equilibration time)
Flow rate: 20 ml / min (small scale) or 40 ml / min (large scale)

MDAP conditions, Examples 36-44
Column: Waters Atlantis, 19 mm x 100 mm; particle size 5 mm
Solvent system: A: aqueous solvent = water + 0.1% trifluoroacetic acid; B: organic solvent = acetonitrile + 0.1% trifluoroacetic acid; make-up solvent = methanol: water 80: 20 + 0.1% formic acid; needle wash solvent = methanol
Methods: Five methods are used depending on the analytical retention time of the target compound. They have a 20-minute runtime (including a 15.5 minute gradient time followed by a 3.5 minute column flush and re-equilibration step).
Method 1.8-2.1 = 0-30% B
Method 2.1-2.6 = 10-45% B
Method 2.6-3.1 = 15-65% B
Method 3.1-4.1 = 30-75% B
Method> 4.1 = 50-100% B (14 minutes, then 5 minutes flash and re-equilibration time)
Flow rate: 20 ml / min
Injection volume: 500ul partial loop injection
Column temperature: normal temperature

Abbreviations DCM: dichloromethane TEA: triethylamine TMS-Cl-: trimethylsilyl chloride DME: dimethyl ether ss: saturated solution TFA: trifluoroacetic acid DAD: diode array detector CD: circular dichroism a / a%: area percentage LC under the curve / Mass Spec: liquid chromatography / mass spectrum NMR: nuclear magnetic resonance SCX: chromatography column provided by Varian ^™ THF: tetrahydrofuran DMSO: dimethyl sulfoxide DMF: dimethylformamide DCM / MDC: dichloromethane / methylene dichloride CDI: 1,1 '-Carbonyldiimidazole LDA: lithium diisopropylamide EDC: 1-ethyl-3- (dimethylaminopropyl) carbodi Imido MsCl: Methanesulfonyl chloride AcOH: Acetic acid HOAt: 1-hydroxy-7-azabenzotriazole HOBt: 1-hydroxybenzotriazole Pd on C: Carbon-supported palladium MeCN: acetonitrile

  In the following procedures, reference is typically made to intermediates or examples by number. These are provided merely to assist one skilled in the art in identifying the starting materials used. The starting material does not necessarily have to be prepared from the batch mentioned. All reactions are performed under an argon atmosphere or can be performed under an argon atmosphere.

ジメチルアミン塩酸塩（２．４５ｇ、３０ｍｍｏｌ）のジクロロメタン（１５０ｍｌ）中懸濁液を、氷／メタノール浴中で冷却し、ついで、トリエチルアミン（６．０ｇ、５９ｍｍｏｌ）、ついで、４−ヨウドベンジルクロライド（８．０ｇ、３０ｍｍｏｌ）で、アルゴン雰囲気下で撹拌しながら処理した。反応混合物を室温にて３０分間撹拌し、ついで、溶液を水（２×１００ｍｌ）で洗浄した。有機層を分離し、硫酸ナトリウムで乾燥し、減圧下で蒸発させて、標題化合物を明褐色固体として得た（７．７３ｇ、９４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２７６（ＥＳ＋）、保持時間２．３０分；Ｃ_９Ｈ_１０ＩＮＯとして計算値２７５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．９７（３Ｈ，ｓ），３．１１（３Ｈ，ｍ），７．１６（２Ｈ，ｍ），７．７５（２Ｈ，ｍ） Intermediate Description Example 1: 4-iodo-N, N-dimethylbenzamide

A suspension of dimethylamine hydrochloride (2.45 g, 30 mmol) in dichloromethane (150 ml) was cooled in an ice / methanol bath, then triethylamine (6.0 g, 59 mmol), then 4-iodobenzyl chloride ( (8.0 g, 30 mmol) with stirring under an argon atmosphere. The reaction mixture was stirred at room temperature for 30 minutes and then the solution was washed with water (2 × 100 ml). The organic layer was separated, dried over sodium sulfate and evaporated under reduced pressure to give the title compound as a light brown solid (7.73 g, 94%).
LC / mass spectrum (ES): found 276 (ES +), retention time 2.30 minutes; calculated 275 as C ₉ H ₁₀ INO
¹ H-NMR (400 MHz, CDCl ₃ ): 2.97 (3H, s), 3.11 (3H, m), 7.16 (2H, m), 7.75 (2H, m)

塩化ピプシルおよびジメチルアミン塩酸塩から、記載例１の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３１２（ＥＳ＋）、保持時間２．８６分；Ｃ_８Ｈ_１０ＩＮＯ_２Ｓとして計算値３１１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．７０（６Ｈ，ｍ），７．４９（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．９１（２Ｈ，ｄ，Ｊ＝８Ｈｚ） Description Example 2: 4-iodo-N, N-dimethylbenzenesulfonamide

The title compound was prepared from pipsyl chloride and dimethylamine hydrochloride using a method similar to that of Description Example 1.
LC / mass spectrum (ES): found 312 (ES +), retention time 2.86 min; calculated 311 as C ₈ H ₁₀ INO ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 2.70 (6H, m), 7.49 (2H, d, J = 8 Hz), 7.91 (2H, d, J = 8 Hz)

４−ブロモフェニル酢酸（９６０ｍｇ、４．４９ｍｍｏｌ）のジクロロメタン（３０ｍｌ）中溶液を、固体１，１’−カルボニルジイミダゾール（７３０ｍｇ、４．５ｍｍｏｌ）で、２０℃アルゴン雰囲気下で撹拌しながら処理した。この混合物を室温にて１５分間撹拌した。トリエチルアミン（０．６３ｍｌ）、ついで、ジメチルアミン塩酸塩（３６７ｍｇ、４．５ｍｍｏｌ）を加え、１時間撹拌し続けた。溶媒の大部分を減圧下で除去し、残渣を２０ｇのＩｓｏｌｕｔｅシリカｓｅｐ−ｐａｋカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を無色の固体として得た（６８９ｍｇ、６４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２４２（ＥＳ＋）、保持時間２．３６分；Ｃ_１０Ｈ_１２ ^７９ＢｒＮＯとして計算値２４１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．９７（３Ｈ，ｓ），３．００（３Ｈ，ｓ），３．６６（２Ｈ，ｓ），７．１２（２Ｈ，ｍ），７．４４（２Ｈ，ｍ） Description Example 3: 2- (4-Bromophenyl) -N, N-dimethylacetamide

A solution of 4-bromophenylacetic acid (960 mg, 4.49 mmol) in dichloromethane (30 ml) was treated with solid 1,1′-carbonyldiimidazole (730 mg, 4.5 mmol) with stirring at 20 ° C. under an argon atmosphere. . The mixture was stirred at room temperature for 15 minutes. Triethylamine (0.63 ml) was added followed by dimethylamine hydrochloride (367 mg, 4.5 mmol) and stirring was continued for 1 hour. Most of the solvent was removed under reduced pressure and the residue was added to a 20 g Isolute silica sep-pak column and eluted with 0-50% ethyl acetate in petroleum ether to give the title compound as a colorless solid (689 mg, 64%).
LC / mass spectrum (ES): found 242 (ES +), retention time 2.36 minutes; calculated 241 as C ₁₀ H ₁₂ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 2.97 (3H, s), 3.00 (3H, s), 3.66 (2H, s), 7.12 (2H, m), 7.44 (2H, m)

４−ヨウド安息香酸メチル（１．４０ｇ、５．３４ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１．２２ｇ、６．４２ｍｍｏｌ）、ヨウ化銅（Ｉ）（１ｍｏｌ％、１０ｍｇ、０．０５ｍｍｏｌ）、ｔｒａｎｓ−１，２−ジアミノシクロヘキサン（１０ｍｏｌ％、６２ｍｇ、０．５４ｍｍｏｌ）および炭酸カリウム（１．５６ｇ、１１．３ｍｍｏｌ）の１，４−ジオキサン（８ｍｌ）中混合物を、マイクロ波反応器において１８０℃で４５分間加熱し、ついで、新たなヨウ化銅（Ｉ）（１ｍｏｌ％、１０ｍｇ、０．０５ｍｍｏｌ）およびｔｒａｎｓ−１，２−ジアミノシクロヘキサン（１０ｍｏｌ％、６２ｍｇ、０．５４ｍｍｏｌ）を加え、反応物を、マイクロ波反応器において１８０℃で１時間４５分間撹拌した。反応混合物を冷却し、５０ｇのプレパックシリカカラムに加え、ついで、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物のクロップを褐色油として得た（６３０ｍｇ、３６％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３２５（ＥＳ＋）、保持時間３．７８分；Ｃ_１６Ｈ_１５Ｆ_３Ｎ_２Ｏ_２として計算値３２４
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．９５（３Ｈ，ｓ），７．６１（２Ｈ，ｍ），８．１５（２Ｈ，ｍ） Description Example 4: 4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl benzoate

Methyl 4-iodobenzoate (1.40 g, 5.34 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (1.22 g, 6.42 mmol), copper iodide (I) (1 mol%, 10 mg, 0.05 mmol), trans-1,2-diaminocyclohexane (10 mol%, 62 mg, 0.54 mmol) and potassium carbonate (1.56 g, 11.3 mmol) in 1,4-dioxane The mixture in (8 ml) was heated in a microwave reactor at 180 ° C. for 45 minutes, then fresh copper (I) iodide (1 mol%, 10 mg, 0.05 mmol) and trans-1,2-diaminocyclohexane ( 10 mol%, 62 mg, 0.54 mmol) and the reaction is heated in a microwave reactor at 180 ° C. It was stirred for 1 hour 45 minutes. The reaction mixture was cooled and added to a 50 g pre-packed silica column, then eluted with 0-50% ethyl acetate in petroleum ether to give a crop of the title compound as a brown oil (630 mg, 36%).
LC / Mass Spec (ES): Found 325 (ES +), retention time 3.78 _{min; C 16 H 15 F 3 N} 2 O 2 Calculated 324
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.68 (4H, m), 3.95 (3H, s), 7.61 (2H, m), 8.15 (2H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸メチル（６００ｍｇ、１．８５ｍｍｏｌ）、水酸化ナトリウム（８１ｍｇ、２．０ｍｍｏｌ）のエタノール（４ｍｌ）および水（４ｍｌ）中溶液を、１時間還流温度で撹拌した。反応混合物を冷却し、エタノールを減圧下で除去し、残渣を、ジエチルエーテル（１０ｍｌ）および水（１０ｍｌ）間で分配した。水層を分離し、２ＮのＨＣｌで酸性化し、ついで、ジクロロメタンで抽出した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、標題化合物をベージュの固体として得た（２２２ｍｇ、３９％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３１１（ＥＳ＋）、保持時間３．２４分；Ｃ_１５Ｈ_１３Ｆ_３Ｎ_２Ｏ_２として計算値３１０
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８５（４Ｈ，ｍ），２．６８（２Ｈ，ｍ），２．７９（２Ｈ，ｍ），７．６７（２Ｈ，ｍ），８．２１（２Ｈ，ｍ） Description Example 5: 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid

4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoate methyl (600 mg, 1.85 mmol), sodium hydroxide (81 mg, 2.0 mmol) Of ethanol in ethanol (4 ml) and water (4 ml) was stirred at reflux for 1 hour. The reaction mixture was cooled, ethanol was removed under reduced pressure, and the residue was partitioned between diethyl ether (10 ml) and water (10 ml). The aqueous layer was separated and acidified with 2N HCl, then extracted with dichloromethane. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give the title compound as a beige solid (222 mg, 39%).
LC / Mass Spec (ES): Found 311 (ES +), retention time 3.24 _{min; C 15 H 13 F 3 N} 2 O 2 Calculated 310
¹ H-NMR (400 MHz, CDCl ₃ ): 1.85 (4H, m), 2.68 (2H, m), 2.79 (2H, m), 7.67 (2H, m), 8.21 (2H, m)

３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（９５０ｍｇ、５．０ｍｍｏｌ）、４−ヨウド安息香酸（１．２４ｇ、５．０ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１０３ｍｇ、１．０ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、９５ｍｇ、０．５ｍｍｏｌ）および炭酸カリウム（１．４５ｇ、１０．５ｍｍｏｌ）のジメチルスルホキシド（１５ｍｌ）中混合物を、油浴中アルゴン雰囲気下１３０℃で３．２５時間撹拌した。反応混合物を減圧下で濾過し、濾液を酢酸エチルおよび水間で分配した。水層を残し、５ＭのＨＣｌでｐＨ２に酸性化した。水性フラクションを酢酸エチルで３回洗浄した。有機層を合し、硫酸ナトリウムで乾燥し、溶媒をロータリーエバポレーションにより除去して、標題化合物を褐色固体として得た（１．６２ｇ、１００％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＭｅＯＤ）：１．８６（４Ｈ，ｍ），２．６６（２Ｈ，ｍ），２．８１（２Ｈ，ｍ），７．６８（２Ｈ，ｄ，Ｊ＝９Ｈｚ），８．１８（２Ｈ，ｄ，Ｊ＝９Ｈｚ） Description Example 5a: 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid

3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (950 mg, 5.0 mmol), 4-iodobenzoic acid (1.24 g, 5.0 mmol), N, N-dimethylglycine (20 mol%, 103 mg, 1.0 mmol), copper (I) iodide (10 mol%, 95 mg, 0.5 mmol) and potassium carbonate (1.45 g, 10.5 mmol) in dimethyl sulfoxide (15 ml) The mixture was stirred at 130 ° C. under an argon atmosphere in the bath for 3.25 hours. The reaction mixture was filtered under reduced pressure and the filtrate was partitioned between ethyl acetate and water. The aqueous layer was left and acidified to pH 2 with 5M HCl. The aqueous fraction was washed 3 times with ethyl acetate. The organic layers were combined, dried over sodium sulfate and the solvent removed by rotary evaporation to give the title compound as a brown solid (1.62 g, 100%).
¹ H-NMR (400 MHz, MeOD): 1.86 (4H, m), 2.66 (2H, m), 2.81 (2H, m), 7.68 (2H, d, J = 9 Hz), 8.18 (2H, d, J = 9Hz)

４−ブロモフェニル酢酸エチル（８７５ｍｇ、３．６０ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（５７０ｍｇ、３．００ｍｍｏｌ）、炭酸カリウム（８４２ｍｇ、６．１０ｍｍｏｌ）、ヨウ化銅（Ｉ）（５ｍｏｌ％、２９ｍｇ、０．１５ｍｍｏｌ）、および（１Ｒ，２Ｒ）−Ｎ，Ｎ’−ジメチル−１，２−シクロヘキサンジアミン（２０ｍｏｌ％、８５ｍｇ、０．６０ｍｍｏｌ）のトルエン（２ｍｌ）中の混合物を、マイクロ波容器においてアルゴン雰囲気下１３０℃で１時間撹拌した。さらにヨウ化銅（Ｉ）（１０ｍｇ、０．０５ｍｍｏｌ）、および（１Ｒ、２Ｒ）−Ｎ，Ｎ’−ジメチル−１，２−シクロヘキサンジアミン（３０ｍｇ、０．２１ｍｍｏｌ）を加え、１３０℃で加熱を計４時間続けた。反応混合物を冷却し、２０ｇのプレパックシリカカラムに加え、０−２０％石油エーテル中酢酸エチルで溶出して、標題化合物を褐色油として得た（０．９２ｇ、８７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３５３（ＥＳ＋）、保持時間３．７０分；Ｃ_１８Ｈ_１９Ｆ_３Ｎ_２Ｏ_２として計算値３５２
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．２６（３Ｈ，ｍ），１．８１（４Ｈ，ｍ），２．６９（４Ｈ，ｍ），３．６６（２Ｈ，ｓ），４．１５（２Ｈ，ｍ），７．３８（２Ｈ，ｍ），７．４５（２Ｈ，ｍ） Description Example 6: Ethyl {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetate

Ethyl 4-bromophenylacetate (875 mg, 3.60 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (570 mg, 3.00 mmol), potassium carbonate (842 mg, 6. 10 mmol), copper (I) iodide (5 mol%, 29 mg, 0.15 mmol), and (1R, 2R) -N, N′-dimethyl-1,2-cyclohexanediamine (20 mol%, 85 mg, 0.60 mmol) Of toluene in toluene (2 ml) was stirred in a microwave vessel at 130 ° C. for 1 hour in an argon atmosphere. Add more copper (I) iodide (10 mg, 0.05 mmol) and (1R, 2R) -N, N′-dimethyl-1,2-cyclohexanediamine (30 mg, 0.21 mmol) and heat at 130 ° C. It lasted for a total of 4 hours. The reaction mixture was cooled, added to a 20 g pre-packed silica column and eluted with 0-20% ethyl acetate in petroleum ether to give the title compound as a brown oil (0.92 g, 87%).
LC / Mass Spec (ES): Found 353 (ES +), retention time 3.70 _{min; C 18 H 19 F 3 N} 2 O 2 Calculated 352
¹ H-NMR (400 MHz, CDCl ₃ ): 1.26 (3H, m), 1.81 (4H, m), 2.69 (4H, m), 3.66 (2H, s), 4.15 (2H, m), 7.38 (2H, m), 7.45 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸エチル（０．９２ｇ、２．６１ｍｍｏｌ）、水酸化ナトリウム（１１４ｍｇ、２．８５ｍｍｏｌ）のエタノール（１０ｍｌ）および水（１０ｍｌ）中混合物を還流温度で１時間撹拌した。反応混合物を冷却し、エタノールを減圧下で除去し、残渣を５ＮのＨＣｌで酸性化し、ついで、ジクロロメタンで溶出した。有機層を５ｇのプレパックカラムに加え、０−１００％石油エーテル中酢酸エチルで溶出して、標題化合物を淡黄色固体として得た（０．４２ｇ、５０％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３２５（ＥＳ＋）、保持時間３．００分；Ｃ_１６Ｈ_１５Ｆ_３Ｎ_２Ｏ_２として計算値３２４
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯＤ_６）：１．７５（４Ｈ，ｍ），２．６０（２Ｈ，ｍ），２．７３（２Ｈ，ｍ），３．６７（２Ｈ，ｓ），７．４３（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．５１（２Ｈ，ｍ），１２．４３（１Ｈ，ｂｓ） Description Example 7: {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid

{4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl acetate (0.92 g, 2.61 mmol), sodium hydroxide (114 mg, A mixture of 2.85 mmol) in ethanol (10 ml) and water (10 ml) was stirred at reflux for 1 hour. The reaction mixture was cooled, ethanol was removed under reduced pressure, the residue was acidified with 5N HCl and then eluted with dichloromethane. The organic layer was added to a 5 g pre-packed column and eluted with 0-100% ethyl acetate in petroleum ether to give the title compound as a pale yellow solid (0.42 g, 50%).
LC / Mass Spec (ES): Found 325 (ES +), retention time 3.00 _{min; C 16 H 15 F 3 N} 2 O 2 Calculated 324
¹ H-NMR (400 MHz, DMSOD ₆ ): 1.75 (4H, m), 2.60 (2H, m), 2.73 (2H, m), 3.67 (2H, s), 7.43 (2H, d, J = 8 Hz), 7.51 (2H, m), 12.43 (1H, bs)

４−（ブロモメチル）安息香酸（２．４３ｇ、１１．３ｍｍｏｌ）のジクロロメタン（４０ｍｌ）中溶液を、固体１，１’−カルボニルジイミダゾール（１．８３ｇ、１１．３ｍｍｏｌ）で処理した。この混合物を室温にて１５分間撹拌した。ピロリジン（０．８ｇ、１１．３ｍｍｏｌ）を加え、撹拌を室温にて１時間続けた。反応混合物を、ジクロロメタンおよび飽和炭酸水素ナトリウム水溶液間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、黄色油を得、これを２０ｇのプレパックシリカカラムに加え、２０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を無色の固体として得た（０．５ｇ、１７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２６８（ＥＳ＋）、保持時間２．４６分；Ｃ_１２Ｈ_１４ ^７９ＢｒＮＯとして計算値２６７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８８（２Ｈ，ｍ），１．９７（２Ｈ，ｍ），３．４３（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．６５（２Ｈ，ｔ，Ｊ＝７Ｈｚ），４．５０（２Ｈ，ｓ），７．４２（２Ｈ，ｄｄ，Ｊ＝７Ｈｚおよび２Ｈｚ），７．５０（２Ｈ，ｄｄ，Ｊ＝７Ｈｚおよび２Ｈｚ） Description Example 8: 1-{[4- (bromomethyl) phenyl] carbonyl} pyrrolidine

A solution of 4- (bromomethyl) benzoic acid (2.43 g, 11.3 mmol) in dichloromethane (40 ml) was treated with solid 1,1′-carbonyldiimidazole (1.83 g, 11.3 mmol). The mixture was stirred at room temperature for 15 minutes. Pyrrolidine (0.8 g, 11.3 mmol) was added and stirring was continued for 1 hour at room temperature. The reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give a yellow oil which was added to a 20 g pre-packed silica column and eluted with 20-50% ethyl acetate in petroleum ether to give the title compound as a colorless oil. Obtained as a solid (0.5 g, 17%).
LC / mass spectrum (ES): found 268 (ES +), retention time 2.46 minutes; calculated 267 as C ₁₂ H ₁₄ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.88 (2H, m), 1.97 (2H, m), 3.43 (2H, t, J = 7 Hz), 3.65 (2H, t, J = 7 Hz), 4.50 (2H, s), 7.42 (2H, dd, J = 7 Hz and 2 Hz), 7.50 (2H, dd, J = 7 Hz and 2 Hz)

２−（４−ブロモフェニル）プロパン酸（２１５ｍｇ、０．９４ｍｍｏｌ）のジクロロメタン（４ｍｌ）中の溶液を、固体１，１’−カルボニルジイミダゾール（１５２ｇ、０．９４ｍｍｏｌ）で処理した。この混合物を室温にて１５分間撹拌した。ピロリジン（６７ｍｇ、０．９４ｍｍｏｌ）を加え、室温にて１時間撹拌を続けた。溶媒の大部分を減圧下で除去し、残渣を５ｇのプレパックシリカカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を無色の固体として得た（１８９ｍｇ、７１％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２８２（ＥＳ＋）、保持時間２．７８分；Ｃ_１３Ｈ_１６ ^７９ＢｒＮＯとして計算値２８１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．４３（３Ｈ，ｄ，Ｊ＝７Ｈｚ），１．７５−１．９３（４Ｈ，ｍ），３．１６（１Ｈ，ｍ），３．３７−３．５６（３Ｈ，ｍ），３．７０（１Ｈ，ｍ），７．１９（２Ｈ，ｍ），７．４３（２Ｈ，ｍ） Description Example 9: 1- [2- (4-Bromophenyl) propanoyl] pyrrolidine

A solution of 2- (4-bromophenyl) propanoic acid (215 mg, 0.94 mmol) in dichloromethane (4 ml) was treated with solid 1,1′-carbonyldiimidazole (152 g, 0.94 mmol). The mixture was stirred at room temperature for 15 minutes. Pyrrolidine (67 mg, 0.94 mmol) was added and stirring was continued at room temperature for 1 hour. Most of the solvent was removed under reduced pressure and the residue was added to a 5 g pre-packed silica column and eluted with 0-50% ethyl acetate in petroleum ether to give the title compound as a colorless solid (189 mg, 71%) .
LC / mass spectrum (ES): found 282 (ES +), retention time 2.78 minutes; calculated 281 as C ₁₃ H ₁₆ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.43 (3H, d, J = 7 Hz), 1.75-1.93 (4H, m), 3.16 (1H, m), 3.37- 3.56 (3H, m), 3.70 (1H, m), 7.19 (2H, m), 7.43 (2H, m)

１−フェニルシクロプロパンカルボン酸およびピロリジンから、記載例８に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値２１６（ＥＳ＋）、保持時間２．４５分；Ｃ_１４Ｈ_１７ＮＯとして計算値２１５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．１４（２Ｈ，ｍ），１．４４（２Ｈ，ｍ），１．７２−１．８１（４Ｈ，ｍ），３．１７（２Ｈ，ｍ），３．４９（２Ｈ，ｍ），７．１９（３Ｈ，ｍ），７．２９（２Ｈ，ｍ） Description Example 10: 1-[(1-phenylcyclopropyl) carbonyl] pyrrolidine

The title compound was prepared from 1-phenylcyclopropanecarboxylic acid and pyrrolidine using a method analogous to that described in Description Example 8.
LC / mass spectrum (ES): found 216 (ES +), retention time 2.45 minutes; calculated 215 as C ₁₄ H ₁₇ NO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.14 (2H, m), 1.44 (2H, m), 1.72-1.81 (4H, m), 3.17 (2H, m) , 3.49 (2H, m), 7.19 (3H, m), 7.29 (2H, m)

１−［（１−フェニルシクロプロピル）カルボニル］ピロリジン（０．７５ｇ、３．４９ｍｍｏｌ）を氷酢酸（１４ｍｌ）中に溶解し、濃硫酸（０．４ｍｌ）、水（１．５ｍｌ）、過ヨウ素酸（１８４ｍｇ、０．８ｍｍｏｌ）、およびヨウ素（３７９ｍｇ、１．４９ｍｍｏｌ）で連続して処理した。この混合物を６０℃で６時間撹拌し、ついで、室温に冷却した。反応混合物を、１０％のメタ亜硫酸水素ナトリウム溶液に加え、酢酸エチルで抽出した。有機層を分離し、無水硫酸ナトリウムで乾燥し、減圧下で蒸発させて、黄色油を得（１．４５ｇ）、これを２０ｇのプレパックシリカカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を黄色油として得た（０．６２ｇ、５２％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３４２（ＥＳ＋）、保持時間２．９４分；Ｃ_１４Ｈ_１６ＩＮＯとして計算値３４１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．１３（２Ｈ，ｍ），１．４３（２Ｈ，ｍ），１．７２−１．８２（４Ｈ，ｍ），３．１７（２Ｈ，ｍ），３．４９（２Ｈ，ｍ），６．９５（２Ｈ，ｍ），７．６１（２Ｈ，ｍ） Description Example 11: 1-{[1- (4-iodophenyl) cyclopropyl] carbonyl} pyrrolidine

1-[(1-Phenylcyclopropyl) carbonyl] pyrrolidine (0.75 g, 3.49 mmol) is dissolved in glacial acetic acid (14 ml), concentrated sulfuric acid (0.4 ml), water (1.5 ml), periodate. Treated sequentially with acid (184 mg, 0.8 mmol) and iodine (379 mg, 1.49 mmol). The mixture was stirred at 60 ° C. for 6 hours and then cooled to room temperature. The reaction mixture was added to a 10% sodium metabisulfite solution and extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and evaporated under reduced pressure to give a yellow oil (1.45 g) which was added to a 20 g pre-packed silica column and added with 0-50% ethyl acetate in petroleum ether. Elution gave the title compound as a yellow oil (0.62 g, 52%).
LC / mass spectrum (ES): found 342 (ES +), retention time 2.94 minutes; calculated 341 as C ₁₄ H ₁₆ INO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.13 (2H, m), 1.43 (2H, m), 1.72-1.82 (4H, m), 3.17 (2H, m) , 3.49 (2H, m), 6.95 (2H, m), 7.61 (2H, m)

３−（４−ブロモフェニル）プロピオン酸（１．０ｇ、４．３７ｍｍｏｌ）のジクロロメタン（３０ｍｌ）中溶液を、固体１，１’−カルボニルジイミダゾール（７０７ｍｇ、４．３６ｍｍｏｌ）で一度に処理した。この混合物を室温で１５分間撹拌した。ジメチルアミン塩酸塩（３６０ｍｇ、４．４２ｍｍｏｌ）、ついで、ジイソプロピルエチルアミン（０．７６ｍｌ、４．４ｍｍｏｌ）を加え、室温にて１時間撹拌を続けた。反応混合物を、ジクロロメタンおよび飽和炭酸水素ナトリウム水溶液間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、標題化合物を無色油として得た（９７２ｍｇ、８７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２５６（ＥＳ＋）、保持時間２．６１分；Ｃ_１１Ｈ_１４ ^７９ＢｒＮＯとして計算値２５５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．５９（２Ｈ，ｔ，Ｊ＝８Ｈｚ），２．９３（８Ｈ，ｍ），７．１１（２Ｈ，ｍ），７．４０（２Ｈ，ｍ） Description Example 12: 3- (4-bromophenyl) -N, N-dimethylpropanamide

A solution of 3- (4-bromophenyl) propionic acid (1.0 g, 4.37 mmol) in dichloromethane (30 ml) was treated in one portion with solid 1,1′-carbonyldiimidazole (707 mg, 4.36 mmol). The mixture was stirred at room temperature for 15 minutes. Dimethylamine hydrochloride (360 mg, 4.42 mmol) was added followed by diisopropylethylamine (0.76 ml, 4.4 mmol) and stirring was continued at room temperature for 1 hour. The reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give the title compound as a colorless oil (972 mg, 87%).
LC / mass spectrum (ES): found 256 (ES +), retention time 2.61 min; calculated 255 as C ₁₁ H ₁₄ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 2.59 (2H, t, J = 8 Hz), 2.93 (8H, m), 7.11 (2H, m), 7.40 (2H, m)

３−（４−ブロモフェニル）プロパン酸およびピロリジンから、クロマトグラフィー精製を行わないことを除いて記載例８に記載の方法と類似の方法を用いて調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値２８２（ＥＳ＋）、保持時間２．７６分；Ｃ_１３Ｈ_１６ ^７９ＢｒＮＯとして計算値２８１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７９−１．９４（４Ｈ，ｍ），２．５３（２Ｈ，ｔ，Ｊ＝８Ｈｚ），２．９４（２Ｈ，ｔ，Ｊ＝８Ｈｚ），３．３０（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．４６（２Ｈ，ｔ，Ｊ＝７Ｈｚ），７．１１（２Ｈ，ｍ），７．４０（２Ｈ，ｍ） Description Example 13: 1- [3- (4-Bromophenyl) propanoyl] pyrrolidine

Prepared from 3- (4-bromophenyl) propanoic acid and pyrrolidine using a method similar to that described in Description 8 except that no chromatographic purification was performed.
LC / mass spectrum (ES): found 282 (ES +), retention time 2.76 minutes; calculated 281 as C ₁₃ H ₁₆ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.79-1.94 (4H, m), 2.53 (2H, t, J = 8 Hz), 2.94 (2H, t, J = 8 Hz), 3.30 (2H, t, J = 7 Hz), 3.46 (2H, t, J = 7 Hz), 7.11 (2H, m), 7.40 (2H, m)

トリエチルアミン（０．２２ｍｌ、１．６ｍｍｏｌ）のジクロロメタン（１０ｍｌ）中溶液を、アセチルクロライド（０．０８ｍｌ、１．１０ｍｍｏｌ）、ついで、４−ブロモ−Ｎ−メチルベンジルアミン（２１０ｍｇ、１．０５ｍｍｏｌ）で処理した。ついで、この混合物を、アルゴン雰囲気下で１０分間撹拌した。反応混合物を水で２回洗浄し、有機層を分離し、硫酸ナトリウムで乾燥し、溶媒をロータリーエバポレーションにより除去して、黄色油を得、これを、０−１００％石油エーテル中酢酸エチルで溶出する５ｇのｓｅｐ−ｐａｋカラムにより精製して、標題化合物を黄色油として得た
ＬＣ／マススペクトル（ＥＳ）：実測値２４２（ＥＳ＋）、保持時間２．３９分；Ｃ_１０Ｈ_１２ ^７９ＢｒＮＯとして計算値２４１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．１４（３Ｈ，ｍ），２．９０（３Ｈ，ｍ），４．５４（２Ｈ，ｍ），７．１３（２Ｈ，ｍ），７．４７（２Ｈ，ｍ） Description Example 14: N-[(4-bromophenyl) methyl] -N-methylacetamide

A solution of triethylamine (0.22 ml, 1.6 mmol) in dichloromethane (10 ml) was added with acetyl chloride (0.08 ml, 1.10 mmol) followed by 4-bromo-N-methylbenzylamine (210 mg, 1.05 mmol). Processed. The mixture was then stirred for 10 minutes under an argon atmosphere. The reaction mixture is washed twice with water, the organic layer is separated, dried over sodium sulfate, and the solvent is removed by rotary evaporation to give a yellow oil, which is 0-100% ethyl acetate in petroleum ether. Purification by eluting 5 g sep-pak column gave the title compound as a yellow oil LC / mass spectrum (ES): found 242 (ES +), retention time 2.39 min; as C ₁₀ H ₁₂ ⁷⁹ BrNO Calculated value 241
¹ H-NMR (400 MHz, CDCl ₃ ): 2.14 (3H, m), 2.90 (3H, m), 4.54 (2H, m), 7.13 (2H, m), 7.47 (2H, m)

２−ピロリジノン（８５０ｍｇ、１０ｍｍｏｌ）のジメチルホルムアミド（４０ｍｌ）中溶液を、アルゴン雰囲気下で撹拌しながら氷／メタノール浴中で冷却した。ついで、水素化ナトリウム（鉱油中６０％、４４０ｍｇ、１１ｍｍｏｌ）の懸濁液を１０分にわたって加えた。反応混合物を３０分冷却しながら撹拌し、ついで、４−ヨウド臭化ベンジル（２．９７ｇ、１０ｍｍｏｌ）を１０分にわたって滴下した。すべての混合物を室温に加温し、ついで、さらに２時間撹拌した。反応混合物を酢酸エチル（１００ｍｌ）、および水（２００ｍｌ）間で分配し、有機層を除去し、減圧下で最小容量にした。残渣を、０−１００％石油エーテル中酢酸エチルで溶出する２０ｇのプレパックシリカカラムのカラムクロマトグラフィーにより精製して、標題化合物を黄色固体として得た（２．９７ｇ、９９％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３０２（ＥＳ＋）、保持時間２．５９分；Ｃ_１１Ｈ_１２ＩＮＯとして計算値３０１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．０１（２Ｈ，ｍ），２．４４（２Ｈ，ｔ，Ｊ＝８Ｈｚ），３．２５（２Ｈ，ｔ，Ｊ＝７Ｈｚ），４．３９（２Ｈ，ｓ），７．００（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．６６（２Ｈ，ｍ） Description Example 15: 1-[(4-iodophenyl) methyl] -2-pyrrolidinone

A solution of 2-pyrrolidinone (850 mg, 10 mmol) in dimethylformamide (40 ml) was cooled in an ice / methanol bath with stirring under an argon atmosphere. A suspension of sodium hydride (60% in mineral oil, 440 mg, 11 mmol) was then added over 10 minutes. The reaction mixture was stirred for 30 minutes with cooling, and then 4-iodobenzyl bromide (2.97 g, 10 mmol) was added dropwise over 10 minutes. All the mixtures were warmed to room temperature and then stirred for another 2 hours. The reaction mixture was partitioned between ethyl acetate (100 ml) and water (200 ml), the organic layer was removed and brought to a minimum volume under reduced pressure. The residue was purified by column chromatography on a 20 g pre-packed silica column eluting with 0-100% ethyl acetate in petroleum ether to give the title compound as a yellow solid (2.97 g, 99%).
LC / mass spectrum (ES): measured value 302 (ES +), retention time 2.59 minutes; calculated value 301 as C ₁₁ H ₁₂ INO
¹ H-NMR (400 MHz, CDCl ₃ ): 2.01 (2H, m), 2.44 (2H, t, J = 8 Hz), 3.25 (2H, t, J = 7 Hz), 4.39 ( 2H, s), 7.00 (2H, d, J = 8 Hz), 7.66 (2H, m)

５−（４−ブロモフェニル）−２−ピロリジノン（ＷＯ００／２１９５８において調製した）（２００ｍｇ、０．８３ｍｍｏｌ）のジメチルホルムアミド（５ｍｌ）中溶液を、水素化ナトリウム（鉱油中６０％、３５ｍｇ、０．８８ｍｍｏｌ）懸濁液で処理した。反応混合物を２０分間撹拌し、ついで、ヨウ化メチル（１２４ｍｇ、０．８８ｍｍｏｌ）を加え、すべての混合物をさらに１８時間撹拌した。反応混合物を数滴の水でクエンチし、ついで、ジクロロメタン（１５ｍｌ）、および水（６０ｍｌ）間で分配し、有機層を除去し、再び水（２×１０ｍｌ）で洗浄し、ついで、減圧下で最小容量にして、標題化合物を褐色油として得た（１４１ｍｇ、６７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２５４（ＥＳ＋）、保持時間２．４１分；Ｃ_１１Ｈ_１２ ^７９ＢｒＮＯとして計算値２５３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８５（１Ｈ，ｍ），２．４０−２．６２（３Ｈ，ｍ），２．６７（３Ｈ，ｓ），４．４８（１Ｈ，ｍ），７．０８（２Ｈ，ｍ），７．５２（２Ｈ，ｍ） Description Example 16: 5- (4-bromophenyl) -1-methyl-2-pyrrolidinone

A solution of 5- (4-bromophenyl) -2-pyrrolidinone (prepared in WO 00/21958) (200 mg, 0.83 mmol) in dimethylformamide (5 ml) was added to sodium hydride (60% in mineral oil, 35 mg,. 88 mmol) treated with suspension. The reaction mixture was stirred for 20 minutes, then methyl iodide (124 mg, 0.88 mmol) was added and all the mixtures were stirred for an additional 18 hours. The reaction mixture was quenched with a few drops of water, then partitioned between dichloromethane (15 ml) and water (60 ml), the organic layer was removed and washed again with water (2 × 10 ml), then under reduced pressure Minimal volume gave the title compound as a brown oil (141 mg, 67%).
LC / mass spectrum (ES): found 254 (ES +), retention time 2.41 min; calculated 253 as C ₁₁ H ₁₂ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.85 (1H, m), 2.40-2.62 (3H, m), 2.67 (3H, s), 4.48 (1H, m) 7.08 (2H, m), 7.52 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メタノール（実施例３０、１．２３ｇ、４．１６ｍｍｏｌ）のジクロロメタン（２０ｍｌ）中溶液に、アルゴン雰囲気下で、トリエチルアミン（０．７５ｍｌ、５．４ｍｍｏｌ）を加え、混合物を室温にて１０分間撹拌した。メタンスルホニルクロライド（０．４２ｍｌ、５．４ｍｍｏｌ）を５分間で滴下し、すべての混合物を室温にて１８時間撹拌した。ついで、反応混合物を水、ついで、飽和炭酸水素ナトリウムで洗浄した。有機層を硫酸ナトリウムで乾燥し、溶媒をロータリーエバポレーションにより除去して、標題化合物を褐色油として得た（１．２４ｇ、９４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３１５（ＥＳ＋）、保持時間３．７４分；Ｃ_１５Ｈ_１４ ^３５ＣｌＦ_３Ｎ_２として計算値３１４
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），４．６３（２Ｈ，ｓ），７．５１（４Ｈ，ｍ） Description Example 17 :: 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

{4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanol (Example 30, 1.23 g, 4.16 mmol) in dichloromethane (20 ml ) Was added triethylamine (0.75 ml, 5.4 mmol) under argon atmosphere and the mixture was stirred at room temperature for 10 minutes. Methanesulfonyl chloride (0.42 ml, 5.4 mmol) was added dropwise over 5 minutes and all the mixtures were stirred at room temperature for 18 hours. The reaction mixture was then washed with water followed by saturated sodium bicarbonate. The organic layer was dried over sodium sulfate and the solvent removed by rotary evaporation to give the title compound as a brown oil (1.24 g, 94%).
LC / Mass Spec (ES): Found 315 (ES +), retention time 3.74 ^{_{min; C 15 H 14 35 ClF 3}} N 2 Calculated 314
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.70 (4H, m), 4.63 (2H, s), 7.51 (4H, m)

モルホリン（６５３ｍｇ、７．５ｍｍｏｌ）のジクロロメタン（４０ｍｌ）中溶液を、氷／メタノール浴中で冷却し、ついで、アルゴン雰囲気下で、トリエチルアミン（７．５ｍｍｏｌ、１．０５ｍｌ）と一緒に撹拌し、ついで、４−ヨウドベンジルクロライド（２．０ｇ、７．５ｍｍｏｌ）を分割して加えた。反応混合物を室温にて０．５時間撹拌し、ついで、溶液を水（２×２０ｍｌ）で洗浄した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、標題化合物を黄色固体として得た（２．４ｇ、１００％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３１８（ＥＳ＋）、保持時間２．３６分；Ｃ_１１Ｈ_１２ＩＮＯ_２として計算値３１７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：３．３２−３．９４（８Ｈ，ｍ），７．１５（２Ｈ，ｍ），７．７７（２Ｈ，ｍ） Description Example 18: 4-[(4-iodophenyl) carbonyl] morpholine

A solution of morpholine (653 mg, 7.5 mmol) in dichloromethane (40 ml) was cooled in an ice / methanol bath and then stirred with triethylamine (7.5 mmol, 1.05 ml) under an argon atmosphere, then 4-iodobenzyl chloride (2.0 g, 7.5 mmol) was added in portions. The reaction mixture was stirred at room temperature for 0.5 h, then the solution was washed with water (2 × 20 ml). The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give the title compound as a yellow solid (2.4 g, 100%).
LC / mass spectrum (ES): found 318 (ES +), retention time 2.36 minutes; calculated 317 as C ₁₁ H ₁₂ INO ₂
¹ H-NMR (400 MHz, CDCl ₃ ): 3.32-3.94 (8H, m), 7.15 (2H, m), 7.77 (2H, m)

４−ヨウドベンゾニトリル（２．４１ｇ、１０．５ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（２．０ｇ、１０．５ｍｍｏｌ）、酸化銅（Ｉ）（２０ｍｏｌ％、２．１ｍｍｏｌ、３００ｍｇ）、Ｎ，Ｎ−ジメチルグリシン（１０．５ｍｍｏｌ、１．０８２ｇ）、および炭酸セシウム（２１ｍｍｏｌ、６．８４ｇ）のジメチルスルホキシド（５ｍｌ）中混合物を、油浴中、１３０℃アルゴン雰囲気下で４時間加熱した。反応混合物を酢酸エチルで希釈した。固体をＫｉｅｓｅｌｇｕｈｒにより濾過した。濾液を酢酸エチルおよび水間で分配した。有機層を分離し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去し、ジエチルエーテルでトリチュレートして、標題化合物を明褐色固体として得た（１．８１２ｇ、５９．５％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２９２（ＥＳ＋）、保持時間３．４３分；Ｃ_１５Ｈ_１２Ｆ_３Ｎ_３として計算値２９１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ）：１．７６（４Ｈ，ｍ），２．６０（２Ｈ，ｍ），２．８２（２Ｈ，ｍ），７．８２（２Ｈ，ｍ），８．１０（２Ｈ，ｍ） Description Example 19: 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzonitrile

4-iodobenzonitrile (2.41 g, 10.5 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (2.0 g, 10.5 mmol), copper oxide (I ) (20 mol%, 2.1 mmol, 300 mg), N, N-dimethylglycine (10.5 mmol, 1.082 g), and cesium carbonate (21 mmol, 6.84 g) in dimethyl sulfoxide (5 ml) The mixture was heated at 130 ° C. under an argon atmosphere for 4 hours. The reaction mixture was diluted with ethyl acetate. The solid was filtered through Kieselguhr. The filtrate was partitioned between ethyl acetate and water. The organic layer was separated and dried over sodium sulfate. The solvent was removed by rotary evaporation and triturated with diethyl ether to give the title compound as a light brown solid (1.812 g, 59.5%).
LC / mass spectrum (ES): found 292 (ES +), retention time 3.43 minutes; calculated 291 as C ₁₅ H ₁₂ F ₃ N ₃
¹ H-NMR (400 MHz, DMSO): 1.76 (4H, m), 2.60 (2H, m), 2.82 (2H, m), 7.82 (2H, m), 8.10 ( 2H, m)

水素化アルミニウムリチウム（１２．４４ｍｌ、ＴＨＦ中２Ｍ溶液、２４．８８ｍｍｏｌ）およびＴＨＦ（３０ｍｌ）を、氷浴中アルゴン雰囲気下で撹拌した。４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］ベンゾニトリル（１．８１２ｇ、６．２２ｍｍｏｌ）のＴＨＦ（３０ｍｌ）中溶液を、１５分にわたって滴下した。ついで、氷浴を除去し、反応混合物を室温にて１．５時間撹拌した。ついで、反応混合物を氷浴を用いて冷却し、水を滴下してクエンチし、溶媒を減圧下で除去した。残渣をＤＣＭおよび水で希釈した。不溶性固体を濾過し、有機層を分離し、ブラインで洗浄し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去した。所望の生成物を、２５ｇのＳＣＸカラムを用いて単離し、ＤＣＭ（３０ｍｌ）、ＤＣＭ／ＭｅＯＨ（６０ｍｌ）、ＭｅＯＨ（３０ｍｌ）で洗浄し、ついで、所望の生成物をＭｅＯＨ中１Ｍアンモニア（２５ｍｌ）で溶出した。溶媒を減圧下で除去して、標題化合物を褐色油として得た（１．５６３ｇ、８５％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２７９（Ｍ−１６，ＥＳ＋），保持時間２．１６分；Ｃ_１５Ｈ_１６Ｆ_３Ｎ_３として計算値２９５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．９３（２Ｈ，ｓ），７．４３（４Ｈ，ｍ） Description Example 20: ({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine

Lithium aluminum hydride (12.44 ml, 2M solution in THF, 24.88 mmol) and THF (30 ml) were stirred in an ice bath under an argon atmosphere. A solution of 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzonitrile (1.812 g, 6.22 mmol) in THF (30 ml) was added to 15 Added dropwise over minutes. The ice bath was then removed and the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was then cooled using an ice bath, quenched by dropwise addition of water and the solvent removed under reduced pressure. The residue was diluted with DCM and water. The insoluble solid was filtered and the organic layer was separated, washed with brine and dried over sodium sulfate. The solvent was removed by rotary evaporation. The desired product is isolated using a 25 g SCX column and washed with DCM (30 ml), DCM / MeOH (60 ml), MeOH (30 ml), then the desired product is 1M ammonia in MeOH (25 ml). Eluted with. The solvent was removed under reduced pressure to give the title compound as a brown oil (1.563 g, 85%).
LC / Mass Spec (ES): Found 279 (M-16, ES + ), retention time 2.16 _{min; C 15 H 16 F 3 N} 3 Calculated 295
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.68 (4H, m), 3.93 (2H, s), 7.43 (4H, m)

３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（３８０ｍｇ、２ｍｍｏｌ）の無水ＤＭＦ（１０ｍｌ）中溶液を、炭酸カリウム（５５２ｍｇ、４ｍｍｏｌ）、ついで、４−ニトロベンジルクロライド（３４３ｍｇ、２ｍｍｏｌ）で処理し、混合物をアルゴン雰囲気下で１６時間室温にて撹拌した。反応混合物を水（２０ｍｌ）および酢酸エチル（２０ｍｌ）間で分離した。有機層を水／ブライン混合物（１：１）（１０ｍｌ）で洗浄し、ついで、硫酸ナトリウムで乾燥し、溶媒を減圧下で除去して、黄色油を得（７５１ｍｇ）、これを、０−２０％石油エーテル中酢酸エチルで溶出する５ｇのプレパックシリカカラムのクロマトグラフィーに付して、標題化合物を黄色油として得た（４１６ｍｇ、６４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３２６（ＥＳ＋）、保持時間３．４４分；Ｃ_１５Ｈ_１４Ｆ_３Ｎ_３Ｏ_２として計算値３２５ Description Example 21: 1-[(4-nitrophenyl) methyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

A solution of 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (380 mg, 2 mmol) in anhydrous DMF (10 ml) was added to potassium carbonate (552 mg, 4 mmol) followed by 4-nitrobenzyl. Treated with chloride (343 mg, 2 mmol) and the mixture was stirred at room temperature for 16 hours under an argon atmosphere. The reaction mixture was separated between water (20 ml) and ethyl acetate (20 ml). The organic layer was washed with a water / brine mixture (1: 1) (10 ml), then dried over sodium sulfate and the solvent removed under reduced pressure to give a yellow oil (751 mg) which was 0-20 Chromatography on a 5 g pre-packed silica column eluting with ethyl acetate in% petroleum ether gave the title compound as a yellow oil (416 mg, 64%).
LC / Mass Spec (ES): Found 326 (ES +), retention time 3.44 _{min; C 15 H 14 F 3 N} 3 O 2 Calculated 325

１−［（４−ニトロフェニル）メチル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（４１０ｍｇ、１．２６ｍｍｏｌ）のメタノール（３ｍｌ）中溶液を、ボロヒドリドナトリウム（９５ｍｇ、２．５０ｍｍｏｌ）を含有する、１０％炭素担持パラジウムの水（１．３ｍｌ）中懸濁液に、アルゴン雰囲気下で冷却し、撹拌しながら加えた。得られた混合物を室温にて１時間撹拌した。反応混合物を濾過し、ついで、２ＭのＨＣｌを用いて酸性化して、過剰のボロヒドリドナトリウムを分解し、ついで、２Ｍ水酸化ナトリウム水溶液を用いて塩基性化した。混合物を酢酸エチルおよび水間で分配した。有機層を硫酸ナトリウムで乾燥し、溶媒を減圧下で除去して、黄色油を得、これを、０−２０％石油エーテル中酢酸エチルで溶出する５ｇのプレパックシリカカラムにより精製して、標題化合物を黄色油として得た（１６６ｍｇ、４３％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２９６（ＥＳ＋）、保持時間２．７０分；Ｃ_１５Ｈ_１６Ｆ_３Ｎ_３として計算値２９５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６４−１．８８（４Ｈ，ｍ），２．４３−２．６８（４Ｈ，ｍ），３．６８（２Ｈ，ｂｓ），５．１２（２Ｈ，ｓ），６．６２（２Ｈ，ｍ），６．９８（２Ｈ，ｍ） Description Example 22: 4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl} aniline

A solution of 1-[(4-nitrophenyl) methyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (410 mg, 1.26 mmol) in methanol (3 ml) To a suspension of 10% palladium on carbon in water (1.3 ml) containing sodium hydride (95 mg, 2.50 mmol) was cooled under argon and added with stirring. The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered and then acidified with 2M HCl to decompose excess sodium borohydride and then basified with 2M aqueous sodium hydroxide. The mixture was partitioned between ethyl acetate and water. The organic layer is dried over sodium sulfate and the solvent is removed under reduced pressure to give a yellow oil which is purified by a 5 g pre-packed silica column eluting with 0-20% ethyl acetate in petroleum ether to give the title compound. Was obtained as a yellow oil (166 mg, 43%).
LC / mass spectrum (ES): found 296 (ES +), retention time 2.70 minutes; calculated 295 as C ₁₅ H ₁₆ F ₃ N ₃
¹ H-NMR (400 MHz, CDCl ₃ ): 1.64-1.88 (4H, m), 2.43-2.68 (4H, m), 3.68 (2H, bs), 5.12 ( 2H, s), 6.62 (2H, m), 6.98 (2H, m)

４−ブロモベンジルイソシアネート（４０８ｍｇ、１．９２ｍｍｏｌ）のアセトニトリル（１５ｍｌ）中溶液を、リエチルアミン（３９０ｍｇ、３．８６ｍｍｏｌ）、ついで、ピロリジン（１３７ｍｇ、１．９３ｍｍｏｌ）で、室温アルゴン雰囲気下で撹拌しながら処理した。反応物を２０℃で３０分間撹拌し、ついで、酢酸エチル（１０ｍｌ）および水（２０ｍｌ）間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、標題化合物を無色の固体として得た（５４２ｍｇ、９９％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２８３（ＥＳ＋）、保持時間２．４２分；Ｃ_１２Ｈ_１５ ^７９ＢｒＮ_２Ｏとして計算値２８２
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．９１（４Ｈ，ｍ），３．４５（４Ｈ，ｍ），４．４９（２Ｈ，ｍ），４．５１（１Ｈ，ｍ），７．２１（２Ｈ，ｍ），７．４４（２Ｈ，ｍ） Description Example 23: N-[(4-bromophenyl) methyl] -1-pyrrolidinecarboxamide

A solution of 4-bromobenzyl isocyanate (408 mg, 1.92 mmol) in acetonitrile (15 ml) was stirred with liethylamine (390 mg, 3.86 mmol) followed by pyrrolidine (137 mg, 1.93 mmol) at room temperature under an argon atmosphere. While processing. The reaction was stirred at 20 ° C. for 30 minutes and then partitioned between ethyl acetate (10 ml) and water (20 ml). The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give the title compound as a colorless solid (542 mg, 99%).
LC / Mass Spec (ES): Found 283 (ES +), retention time 2.42 ^{_{min; C 12 H 15 79 BrN 2}} O Calculated 282
¹ H-NMR (400 MHz, CDCl ₃ ): 1.91 (4H, m), 3.45 (4H, m), 4.49 (2H, m), 4.51 (1H, m), 7.21 (2H, m), 7.44 (2H, m)

Ｎ−［（４−ブロモフェニル）メチル］−１−ピロリジンカルボキサミド（２３０ｍｇ、０．８１ｍｍｏｌ）を、ジメチルホルムアミド（２ｍｌ）中で溶解し、室温にて、６０％水素化ナトリウムの鉱油（３３ｍｇ、０．８３ｍｍｏｌ）中懸濁液で処理した。この混合物を、１５分間撹拌し、ついで、ヨウドメタン（１１６ｍｇ、０．８２ｍｍｏｌ）で処理した。得られた混合物を２０℃で１６．５時間撹拌した。反応物を水（４ｍｌ）でクエンチし、酢酸エチル（４ｍｌ）で抽出した。有機層を硫酸ナトリウムで乾燥し、溶媒を減圧下で除去して、標題化合物を無色油として得た（２５０ｍｇ、粗）。ＬＣ／マススペクトル（ＥＳ）：実測値２９７（ＥＳ＋）、保持時間２．９０分；Ｃ_１３Ｈ_１７ ^７９ＢｒＮ_２Ｏとして計算値２９６ Description Example 24: N-[(4-bromophenyl) methyl] -N-methyl-1-pyrrolidine carboxamide

N-[(4-Bromophenyl) methyl] -1-pyrrolidinecarboxamide (230 mg, 0.81 mmol) was dissolved in dimethylformamide (2 ml) and at room temperature 60% sodium hydride mineral oil (33 mg, 0 .83 mmol) in suspension. The mixture was stirred for 15 minutes and then treated with iodomethane (116 mg, 0.82 mmol). The resulting mixture was stirred at 20 ° C. for 16.5 hours. The reaction was quenched with water (4 ml) and extracted with ethyl acetate (4 ml). The organic layer was dried over sodium sulfate and the solvent removed under reduced pressure to give the title compound as a colorless oil (250 mg, crude). LC / mass spectrum (ES): found 297 (ES +), retention time 2.90 minutes; calculated 296 as C ₁₃ H ₁₇ ⁷⁹ BrN ₂ O

４−ブロモ−メチルベンジルアミン（２．０ｇ、１０ｍｍｏｌ）およびトリエチルアミン（２ｇ、２０ｍｍｏｌ、２．８ｍｌ）のジクロロメタン（４０ｍｌ）中溶液に、アセチルクロライド（０．８６ｇ、１１ｍｍｏｌ、０．７８ｍｌ）を、アルゴン雰囲気下で撹拌しながら滴下し、混合物をすべて２０℃で０．５時間撹拌した。反応混合物を水で２回洗浄し（各々３０ｍｌ）、有機層を硫酸ナトリウムで乾燥し、溶媒を減圧下で除去して、標題化合物を黄色固体として得た（２．２７ｇ、９４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２４２（ＥＳ＋）、保持時間２．２４分；Ｃ_１０Ｈ_１２ ^７９ＢｒＮＯとして計算値２４１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．４６（３Ｈ，ｄ，Ｊ＝７Ｈｚ），１．９９（３Ｈ，ｓ），５．０８（１Ｈ，ｍ），５．６７（１Ｈ．Ｍ），７．１９（２Ｈ，ｍ），７．４６（２Ｈ，ｍ） Description Example 25: N- [1- (4-bromophenyl) ethyl] acetamide

To a solution of 4-bromo-methylbenzylamine (2.0 g, 10 mmol) and triethylamine (2 g, 20 mmol, 2.8 ml) in dichloromethane (40 ml) was added acetyl chloride (0.86 g, 11 mmol, 0.78 ml) to argon. The mixture was added dropwise with stirring under an atmosphere, and the whole mixture was stirred at 20 ° C. for 0.5 hour. The reaction mixture was washed twice with water (30 ml each), the organic layer was dried over sodium sulfate, and the solvent was removed under reduced pressure to give the title compound as a yellow solid (2.27 g, 94%).
LC / mass spectrum (ES): found 242 (ES +), retention time 2.24 minutes; calculated 241 as C ₁₀ H ₁₂ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.46 (3H, d, J = 7 Hz), 1.99 (3H, s), 5.08 (1H, m), 5.67 (1H.M) 7.19 (2H, m), 7.46 (2H, m)

Ｎ−［１−（４−ブロモフェニル）エチル］アセトアミドおよびヨウドメタンから、記載例２４に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値２５７（ＥＳ＋）、保持時間２．５３分；Ｃ_１１Ｈ_１４ ^７９ＢｒＮＯとして計算値２５６ Description Example 26: N- [1- (4-bromophenyl) ethyl] -N-methylacetamide

The title compound was prepared from N- [1- (4-bromophenyl) ethyl] acetamide and iodomethane in a manner similar to that described in Description 24.
LC / mass spectrum (ES): found 257 (ES +), retention time 2.53 minutes; calculated 256 as C ₁₁ H ₁₄ ⁷⁹ BrNO

２−（４−ブロモフェニル）ピロリジンおよびアセチルクロライドから、記載例２５に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値２６８（ＥＳ＋）、保持時間２．５９分；Ｃ_１２Ｈ_１４ ^７９ＢｒＮＯとして計算値２６７ Description Example 27: 1-acetyl-2- (4-bromophenyl) pyrrolidine

The title compound was prepared from 2- (4-bromophenyl) pyrrolidine and acetyl chloride using a method analogous to that described in Description 25.
LC / mass spectrum (ES): found 268 (ES +), retention time 2.59 minutes; calculated 267 as C ₁₂ H ₁₄ ⁷⁹ BrNO

４−ブロモベンジルアミン（１．８５ｇ、１０ｍｍｏｌ）およびトリエチルアミン（２ｇ、２０ｍｍｏｌ）のジメチルホルムアミド（３０ｍｌ）中溶液を、３−クロロプロパンスルホニルクロライド（１．７８ｇ、１０ｍｍｏｌ）を１０分にわたってアルゴン雰囲気下で撹拌しながら滴下することにより処理した。この混合物を３０分間撹拌し、ついで、鉱油中６０％の水素化ナトリウム（１．２ｇ、３０ｍｍｏｌのＮａＨ）で処理し、混合物をすべて室温にて３日間撹拌した。反応混合物を、水（５０ｍｌ）およびジクロロメタン（３０ｍｌ）間で分配した。有機層を硫酸ナトリウムで乾燥し、ロータリーエバポレーションにより最小容量に減少した。残渣を、２０ｇのプレパックシリカカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を黄色油として得た（２．７２ｇ、９４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２９０（ＥＳ＋）、保持時間２．６８分；Ｃ_１０Ｈ_１２ ^７９ＢｒＮＯ_２Ｓとして計算値２８９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：２．３２（２Ｈ，ｍ），３．１１（２Ｈ，ｍ），３．２１（２Ｈ，ｍ），３．１３（２Ｈ，ｓ），７．２４（２Ｈ，ｍ），７．４９（２Ｈ，ｍ） Description Example 28: 2-[(4-Bromophenyl) methyl] isothiazolidine 1,1-dioxide

A solution of 4-bromobenzylamine (1.85 g, 10 mmol) and triethylamine (2 g, 20 mmol) in dimethylformamide (30 ml) was stirred with 3-chloropropanesulfonyl chloride (1.78 g, 10 mmol) for 10 minutes under an argon atmosphere. It was processed by adding dropwise. The mixture was stirred for 30 minutes and then treated with 60% sodium hydride in mineral oil (1.2 g, 30 mmol NaH) and the mixture was all stirred at room temperature for 3 days. The reaction mixture was partitioned between water (50 ml) and dichloromethane (30 ml). The organic layer was dried over sodium sulfate and reduced to minimum volume by rotary evaporation. The residue was added to a 20 g pre-packed silica column and eluted with 0-50% ethyl acetate in petroleum ether to give the title compound as a yellow oil (2.72 g, 94%).
LC / mass spectrum (ES): found 290 (ES +), retention time 2.68 minutes; calculated as 289 C ₁₀ H ₁₂ ⁷⁹ BrNO ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 2.32 (2H, m), 3.11 (2H, m), 3.21 (2H, m), 3.13 (2H, s), 7.24 (2H, m), 7.49 (2H, m)

４−ブロモフェネチルアミンおよび４−クロロブチリルクロライドから、記載例２８に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値２６８（ＥＳ＋）、保持時間２．５０分；Ｃ_１２Ｈ_１４ ^７９ＢｒＮＯとして計算値２６７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．９６（２Ｈ，ｍ），２．３５（２Ｈ，ｔ，Ｊ＝８Ｈｚ），２．８０（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．２６（２Ｈ，ｍ），３．５１（２Ｈ，ｍ），７．１０（２Ｈ，ｍ），７．４２（２Ｈ，ｍ） Description Example 29: 1- [2- (4-bromophenyl) ethyl] -2-pyrrolidinone

The title compound was prepared from 4-bromophenethylamine and 4-chlorobutyryl chloride using a method analogous to that described in Description Example 28.
LC / mass spectrum (ES): found 268 (ES +), retention time 2.50 minutes; calculated 267 as C ₁₂ H ₁₄ ⁷⁹ BrNO
¹ H-NMR (400 MHz, CDCl ₃ ): 1.96 (2H, m), 2.35 (2H, t, J = 8 Hz), 2.80 (2H, t, J = 7 Hz), 3.26 ( 2H, m), 3.51 (2H, m), 7.10 (2H, m), 7.42 (2H, m)

（２−メチルプロピル）アミン（１２１ｍｇ、１．６５ｍｍｏｌ）およびトリエチルアミン（０．３５ｍｌ、２．４７ｍｍｏｌ）のＤＣＭ（１０ｍｌ）中溶液を、４−ヨウドベンゼンスルホニルクロライド（５００ｍｇ、１．６５ｍｍｏｌ）をアルゴン雰囲気下で撹拌しながら１０分にわたって滴下して処理した。反応混合物を室温にて１６時間撹拌した。ついで、反応混合物を水（１０ｍｌ）で洗浄し、有機層を分離し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去して、標題化合物白色固体として得た（５１７ｍｇ、９２％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３４０（ＥＳ＋）、保持時間３．１４分；Ｃ_１０Ｈ_１４ＩＮＯ_２Ｓとして計算値３３９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：０．８８（６Ｈ，ｍ），１．７２（１Ｈ，ｍ），２．７８（２Ｈ，ｍ），４．４１（１Ｈ，ｍ）７．５６（２Ｈ，ｍ），７．８８（２Ｈ，ｍ） Description Example 30: 4-iodo-N- (2-methylpropyl) benzenesulfonamide

A solution of (2-methylpropyl) amine (121 mg, 1.65 mmol) and triethylamine (0.35 ml, 2.47 mmol) in DCM (10 ml) and 4-iodobenzenesulfonyl chloride (500 mg, 1.65 mmol) in an argon atmosphere Treated dropwise over 10 minutes with stirring under. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was then washed with water (10 ml) and the organic layer was separated and dried over sodium sulfate. The solvent was removed by rotary evaporation to give the title compound as a white solid (517 mg, 92%).
LC / mass spectrum (ES): found 340 (ES +), retention time 3.14 min; calculated as 339 C ₁₀ H ₁₄ INO ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 0.88 (6H, m), 1.72 (1H, m), 2.78 (2H, m), 4.41 (1H, m) 7.56 ( 2H, m), 7.88 (2H, m)

４−ヨウドベンゼンスルホニルクロライドおよびピロリジンから、記載例３０に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３３８（ＥＳ＋）、保持時間２．９５分；Ｃ_１０Ｈ_１２ＩＮＯ_２Ｓとして計算値３３７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７６（４Ｈ，ｍ），３．２１（４Ｈ，ｍ），７．５３（２Ｈ，ｍ），７．８８（２Ｈ，ｍ） Description Example 31: 1-[(4-iodophenyl) sulfonyl] pyrrolidine

The title compound was prepared from 4-iodobenzenesulfonyl chloride and pyrrolidine using a method analogous to that described in Description Example 30.
LC / mass spectrum (ES): found 338 (ES +), retention time 2.95 minutes; calculated 337 as C ₁₀ H ₁₂ INO ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 1.76 (4H, m), 3.21 (4H, m), 7.53 (2H, m), 7.88 (2H, m)

モルホリンおよび４−ヨウドベンゼンスルホニルクロライドから、記載例３０に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３５４（ＥＳ＋）、保持時間２．８３分；Ｃ_１０Ｈ_１２ＩＮＯ_３Ｓとして計算値３５３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：３．００（４Ｈ，ｍ），３．７５（４Ｈ，ｍ），７．４６（２Ｈ，ｍ），７．９２（２Ｈ，ｍ） Description Example 32: 4-[(4-iodophenyl) sulfonyl] morpholine

The title compound was prepared from morpholine and 4-iodobenzenesulfonyl chloride using a method analogous to that described in Description Example 30.
LC / mass spectrum (ES): found 354 (ES +), retention time 2.83 minutes; calculated 353 as C ₁₀ H ₁₂ INO ₃ S
¹ H-NMR (400 MHz, CDCl ₃ ): 3.00 (4H, m), 3.75 (4H, m), 7.46 (2H, m), 7.92 (2H, m)

［２−（メチルオキシ）エチル］アミンおよび４−ヨウドベンゼンスルホニルクロライドから、記載例３０に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３４２（ＥＳ＋）、保持時間２．６１分；Ｃ_９Ｈ_１２ＩＮＯ_３Ｓとして計算値３４１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：３．１０（２Ｈ，ｍ），３．２７（３Ｈ，ｓ），３．４０（２Ｈ，ｍ），４．８６（１Ｈ，ｍ），７．５６（２Ｈ，ｍ），７．８７（２Ｈ，ｍ） Description Example 33: 4-iodo-N- [2- (methyloxy) ethyl] benzenesulfonamide

The title compound was prepared from [2- (methyloxy) ethyl] amine and 4-iodobenzenesulfonyl chloride using a method analogous to that described in Description Example 30.
LC / mass spectrum (ES): found 342 (ES +), retention time 2.61 minutes; calculated 341 as C ₉ H ₁₂ INO ₃ S
¹ H-NMR (400 MHz, CDCl ₃ ): 3.10 (2H, m), 3.27 (3H, s), 3.40 (2H, m), 4.86 (1H, m), 7.56 (2H, m), 7.87 (2H, m)

［２−（１−ピロリジニル）エチル］アミンおよび４−ヨウドベンゼンスルホニルクロライドから、記載例３０に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３８１（ＥＳ＋）、保持時間１．６９分；Ｃ_１２Ｈ_１７ＩＮ_２Ｏ_２Ｓとして計算値３８０ Description Example 34: 4-iodo-N- [2- (1-pyrrolidinyl) ethyl] benzenesulfonamide

The title compound was prepared from [2- (1-pyrrolidinyl) ethyl] amine and 4-iodobenzenesulfonyl chloride using a method analogous to that described in Description 30.
LC / mass spectrum (ES): found 381 (ES +), retention time 1.69 minutes; calculated 380 as C ₁₂ H ₁₇ IN ₂ O ₂ S

（テトラヒドロ−２−フラニルメチル）アミンおよび４−ヨウドベンゼンスルホニルクロライドから、記載例３０に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３６８（ＥＳ＋）、保持時間２．７０分；Ｃ_１１Ｈ_１４ＩＮＯ_３Ｓとして計算値３６７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６０（１Ｈ，ｍ），１．８３２．０（３Ｈ，ｍ），２．８８（１Ｈ，ｍ），３．１３（１Ｈ，ｍ），３．７０（１Ｈ，ｍ），３．７７（１Ｈ，ｍ），３．９３（１Ｈ，ｍ），４．８３（１Ｈ，ｍ），７．５５（２Ｈ，ｍ），７．８６（２Ｈ，ｍ） Description Example 35: 4-iodo-N- (tetrahydro-2-furanylmethyl) benzenesulfonamide

The title compound was prepared from (tetrahydro-2-furanylmethyl) amine and 4-iodobenzenesulfonyl chloride using a method analogous to that described in Description Example 30.
LC / mass spectrum (ES): found 368 (ES +), retention time 2.70 min; calculated as C ₁₁ H ₁₄ INO ₃ S 367
¹ H-NMR (400 MHz, CDCl ₃ ): 1.60 (1H, m), 1.832.0 (3H, m), 2.88 (1H, m), 3.13 (1H, m), 3 .70 (1H, m), 3.77 (1H, m), 3.93 (1H, m), 4.83 (1H, m), 7.55 (2H, m), 7.86 (2H, m)

ＨＡＴＵ（Ｏ−（７−アザベンゾトリアゾール−１−イル）−Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルウロニウムヘキサフルオロホスフェート）（１．７５ｇ；４．６０ｍｍｏｌ）を、１−メチル−１Ｈ−イミダゾール−２−カルボン酸（５０９ｍｇ；４．０４ｍｍｏｌ）、Ｎ，Ｏ−ジメチルヒドロキシルアミン塩酸塩（３９１ｍｇ；４．０１ｍｍｏｌ）、およびジイソプロピルエチルアミン（２．０ｍＬ；１１．９ｍｍｏｌ）の無水ＤＭＦ（１４ｍＬ）中撹拌溶液に分割して加えた。混合物を室温にて１７時間撹拌し、酢酸エチル（１００ｍＬ）および水（１００ｍＬ）間で分配した。有機相を乾燥（ＭｇＳＯ_４）し、減圧下で濃縮し、無色の油を得た（１．４５ｇ）。これをカラムクロマトグラフィーにより精製して、標題化合物を無色油として得た（４９４ｍｇ；７３％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：３．５７（３Ｈ，ｂｒｓ），３．８６（３Ｈ，ｓ），３．９１（３Ｈ，ｓ），６．９７（１Ｈ，ｄ，Ｊ＝１Ｈｚ），７．０７（１Ｈ，ｄ，Ｊ＝１Ｈｚ） Description Example 36: N, 1-dimethyl-N- (methyloxy) -1H-imidazole-2-carboxamide

HATU (O- (7-azabenzotriazol-1-yl) -N, N, N ′, N′-tetramethyluronium hexafluorophosphate) (1.75 g; 4.60 mmol) was converted to 1-methyl-1H. -Imidazole-2-carboxylic acid (509 mg; 4.04 mmol), N, O-dimethylhydroxylamine hydrochloride (391 mg; 4.01 mmol), and diisopropylethylamine (2.0 mL; 11.9 mmol) in anhydrous DMF (14 mL) Add in portions to a medium stirring solution. The mixture was stirred at room temperature for 17 hours and partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase was dried (MgSO ₄ ) and concentrated under reduced pressure to give a colorless oil (1.45 g). This was purified by column chromatography to give the title compound as a colorless oil (494 mg; 73%).
¹ H-NMR (400 MHz, CDCl ₃ ): 3.57 (3H, brs), 3.86 (3H, s), 3.91 (3H, s), 6.97 (1H, d, J = 1 Hz) , 7.07 (1H, d, J = 1 Hz)

ジフェニルホスホリルアジド（２９０μＬ；１．３６ｍｍｏｌ）を、４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（１９５ｍｇ；０．６３ｍｍｏｌ）およびジイソプロピルエチルアミン（２２０μＬ；１．２９ｍｍｏｌ）の１，４−ジオキサン（２．２ｍＬ）中撹拌混合物に加えた。混合物を２時間加熱還流し、ピロリジン（１００μＬ；１．２１ｍｍｏｌ）を加え、反応物をさらに１時間加熱還流した。減圧下で濃縮し、ついで、カラムクロマトグラフィーにより精製して、標題化合物を得た（３８ｍｇ；１６％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３７９（ＥＳ＋）、保持時間３．１８分；Ｃ_１９Ｈ_２１Ｆ_３Ｎ_４Ｏとして計算値３７８
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６７−１．７７（４Ｈ，ｍ），１．８３−２．０３（４Ｈ，ｍ），２．６８−２．７７（４Ｈ，ｍ），３．４０−３．５４（４Ｈ，ｍ），６．３４（１Ｈ，ｓ），７．３４−７．４０（２Ｈ，ｍ），７．５０−７．５５（２Ｈ，ｍ） Description Example 37: N- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide

Diphenylphosphoryl azide (290 μL; 1.36 mmol) was added to 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid (195 mg; 0.63 mmol). And diisopropylethylamine (220 μL; 1.29 mmol) in 1,4-dioxane (2.2 mL) was added to the stirred mixture. The mixture was heated to reflux for 2 hours, pyrrolidine (100 μL; 1.21 mmol) was added and the reaction was heated to reflux for an additional hour. Concentrated under reduced pressure and then purified by column chromatography to give the title compound (38 mg; 16%).
LC / mass spectrum (ES): found 379 (ES +), retention time 3.18 min; calculated as 378 as C ₁₉ H ₂₁ F ₃ N ₄ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.67-1.77 (4H, m), 1.83 to 2.03 (4H, m), 2.68-2.77 (4H, m), 3.40-3.54 (4H, m), 6.34 (1H, s), 7.34-7.40 (2H, m), 7.50-7.55 (2H, m)

４−ヨウド−Ｎ，Ｎ−ジメチルベンズアミド（１００ｍｇ、０．３６ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（８３ｍｇ、０．４４ｍｍｏｌ）、ヨウ化銅（Ｉ）（１ｍｏｌ％、０．７ｍｇ、０．００３６ｍｍｏｌ）、ｔｒａｎｓ−１，２−ジアミノシクロヘキサン（１０ｍｏｌ％、４ｍｇ、０．０３６ｍｍｏｌ）および炭酸カリウム（１０５ｍｇ、０．７６ｍｍｏｌ）の１，４−ジオキサン（０．５ｍｌ）中混合物を、マイクロ波容器中１８０℃で１５分間撹拌し、ついで、新たなヨウ化銅（Ｉ）（１ｍｏｌ％、０．７ｍｇ、０．００３６ｍｍｏｌ）およびｔｒａｎｓ−１，２−ジアミノシクロヘキサン（１０ｍｏｌ％、４ｍｇ、０．０３６ｍｍｏｌ）を加え、反応物をマイクロ波容器中１８０℃で２０分間撹拌した。ついで、新たなヨウ化銅（Ｉ）（１ｍｏｌ％、０．７ｍｇ、０．００３６ｍｍｏｌ）およびｔｒａｎｓ−１，２−ジアミノシクロヘキサン（１０ｍｏｌ％、４ｍｇ、０．０３６ｍｍｏｌ）を加え、反応物を、マイクロ波容器中１８０℃で３０分間撹拌した。反応混合物を冷却し、５ｇのプレパックシリカカラムに加え、これを酢酸エチルから溶出して、生成物をさらにマス・ディレクテッド自動精製により精製して、標題化合物のクロップを褐色油として得た（５３ｍｇ、４３％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３３８（ＥＳ＋）、保持時間３．０９分；Ｃ_１７Ｈ_１８Ｆ_３Ｎ_３Ｏとして計算値３３７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），３．００（３Ｈ，ｓ），３．１４（３Ｈ，ｓ），７．５４（４Ｈ，ｍ） Example 1: N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

4-iodo-N, N-dimethylbenzamide (100 mg, 0.36 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (83 mg, 0.44 mmol), copper iodide (I) (1 mol%, 0.7 mg, 0.0036 mmol), trans-1,2-diaminocyclohexane (10 mol%, 4 mg, 0.036 mmol) and potassium carbonate (105 mg, 0.76 mmol) in 1,4-dioxane The mixture in (0.5 ml) was stirred in a microwave vessel at 180 ° C. for 15 minutes, then fresh copper (I) iodide (1 mol%, 0.7 mg, 0.0036 mmol) and trans-1,2- Diaminocyclohexane (10 mol%, 4 mg, 0.036 mmol) was added and the reaction was microwaved. It was stirred at 180 ° C. 20 min in. Then fresh copper (I) iodide (1 mol%, 0.7 mg, 0.0036 mmol) and trans-1,2-diaminocyclohexane (10 mol%, 4 mg, 0.036 mmol) were added and the reaction was microwaved. The mixture was stirred at 180 ° C. for 30 minutes in the container. The reaction mixture was cooled and added to a 5 g pre-packed silica column, eluting from ethyl acetate, and the product was further purified by mass directed autopurification to give a crop of the title compound as a brown oil (53 mg 43%).
LC / mass spectrum (ES): found 338 (ES +), retention time 3.09 minutes; calculated 337 as C ₁₇ H ₁₈ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.70 (4H, m), 3.00 (3H, s), 3.14 (3H, s), 7.54 (4H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（８７ｍｇ、０．２８ｍｍｏｌ）のジクロロメタン（３ｍｌ）中溶液を、固体１，１’−カルボニルジイミダゾール（４６ｍｇ、０．２８ｍｍｏｌ）で処理した。この混合物を室温で１５分間撹拌した。ピロリジン（２３ｍｇ、０．３２ｍｍｏｌ）を加え、室温にて１時間撹拌を続けた。反応混合物を５ｇのプレパックシリカカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を黄色油として得た（５１ｍｇ、５０％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３６４（ＥＳ＋）、保持時間３．２２分；Ｃ_１９Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３６３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），１．９１（２Ｈ，ｍ），１．９８（２Ｈ，ｍ），２．７０（４Ｈ，ｍ），３．４３（２Ｈ，ｔ，Ｊ＝６Ｈｚ），３．６７（２Ｈ，ｔ，Ｊ＝６Ｈｚ），７．５３（２Ｈ，ｍ），７．６４（２Ｈ，ｍ） Example 2: 1- [4- (1-Pyrrolidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

A solution of 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid (87 mg, 0.28 mmol) in dichloromethane (3 ml) was added to a solid 1, Treated with 1′-carbonyldiimidazole (46 mg, 0.28 mmol). The mixture was stirred at room temperature for 15 minutes. Pyrrolidine (23 mg, 0.32 mmol) was added and stirring was continued at room temperature for 1 hour. The reaction mixture was added to a 5 g pre-packed silica column and eluted with 0-50% ethyl acetate in petroleum ether to give the title compound as a yellow oil (51 mg, 50%).
LC / mass spectrum (ES): found 364 (ES +), retention time 3.22 min; calculated as C ₁₉ H ₂₀ F ₃ N ₃ O 363
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 1.91 (2H, m), 1.98 (2H, m), 2.70 (4H, m), 3.43 (2H, t, J = 6 Hz), 3.67 (2H, t, J = 6 Hz), 7.53 (2H, m), 7.64 (2H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸およびＮ−メチルベンジルアミンから、実施例２に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４１４（ＥＳ＋）、保持時間３．７１分；Ｃ_２３Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値４１３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６９（４Ｈ，ｍ），２．８８および３．０７（３Ｈ，ｓ（回転異性体）），４．５２および４．７７（２Ｈ，ｓ（回転異性体）），７．１７（１Ｈ，ｍ），７．３４（４Ｈ，ｍ），７．５５（４Ｈ，ｍ） Example 3: N-methyl-N- (phenylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

A method analogous to that described in Example 2 from 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid and N-methylbenzylamine Was used to prepare the title compound.
LC / mass spectrum (ES): found 414 (ES +), retention time 3.71 min; calculated 413 as C ₂₃ H ₂₂ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.69 (4H, m), 2.88 and 3.07 (3H, s (rotamers)), 4.52 And 4.77 (2H, s (rotamers)), 7.17 (1H, m), 7.34 (4H, m), 7.55 (4H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸およびＮ−エチルメチルアミンから、実施例２に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３５２（ＥＳ＋）、保持時間３．２２分；Ｃ_１８Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３５１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．０７−１．２８（３Ｈ，ｍ（回転異性体）），１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），２．９６および３．０９（３Ｈ，ｍ（回転異性体）），３．３１および３．６１（２Ｈ，ｍ（回転異性体）），７．５３（４Ｈ，ｍ） Example 4: N-ethyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

A method similar to that described in Example 2 from 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid and N-ethylmethylamine Was used to prepare the title compound.
LC / mass spectrum (ES): found 352 (ES +), retention time 3.22 min; calculated 351 as C ₁₈ H ₂₀ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.07-1.28 (3H, m (rotamer)), 1.83 (4H, m), 2.70 (4H, m), 2.96 And 3.09 (3H, m (rotamers)), 3.31 and 3.61 (2H, m (rotamers)), 7.53 (4H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸およびＮ−メチルブチルアミンから、実施例２に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３８０（ＥＳ＋）、保持時間３．５４分；Ｃ_２０Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値３７９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：０．８１−１．０１（３Ｈ，ｍ（回転異性体）），１．１７および１．４２（２Ｈ，ｍ（回転異性体）），１．５３−１．６３（２Ｈ，ｍ）１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），２．９５および３．０９（３Ｈ，ｍ（回転異性体）），３．２４および３．５５（２Ｈ，ｍ（回転異性体）），７．５３（４Ｈ，ｍ） Example 5: N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

A method similar to that described in Example 2 was prepared from 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid and N-methylbutylamine. Was used to prepare the title compound.
LC / mass spectrum (ES): found 380 (ES +), retention time 3.54 minutes; calculated as 379 as C ₂₀ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 0.81-1.01 (3H, m (rotamers)), 1.17 and 1.42 (2H, m (rotamers)), 1.53 -1.63 (2H, m) 1.83 (4H, m), 2.70 (4H, m), 2.95 and 3.09 (3H, m (rotamer)), 3.24 and 3 .55 (2H, m (rotamer)), 7.53 (4H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸およびＮ−メチルフェネチルアミンから、実施例２に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４２８（ＥＳ＋）、保持時間３．７０分；Ｃ_２４Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値４２７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．８３（３Ｈ，ｓ），３．００および３．１６（２Ｈ，ｍ（回転異性体）），３．５１および３．８０（２Ｈ，ｍ（回転異性体）），６．９８（１Ｈ，ｍ），７．１２（１Ｈ，ｍ），７．２８（４Ｈ，ｍ），７．４３（２Ｈ，ｍ），７．５２（１Ｈ，ｍ） Example 6: N-methyl-N- (2-phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

A method similar to that described in Example 2 was prepared from 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid and N-methylphenethylamine. Was used to prepare the title compound.
LC / Mass Spec (ES): Found 428 (ES +), retention time 3.70 _{min; C 24 H 24 F 3 N} 3 O Calculated 427
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.68 (4H, m), 2.83 (3H, s), 3.00 and 3.16 (2H, m ( Rotamers)), 3.51 and 3.80 (2H, m (rotamers)), 6.98 (1H, m), 7.12 (1H, m), 7.28 (4H, m) , 7.43 (2H, m), 7.52 (1H, m)

４−ヨウド−Ｎ，Ｎ−ジメチルベンゼンスルホンアミド（１５６ｍｇ、０．５ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１０５ｍｇ、０．５５ｍｍｏｌ）、ヨウ化銅（Ｉ）（１ｍｏｌ％、１ｍｇ、０．００５ｍｍｏｌ）、ｔｒａｎｓ−１，２−ジアミノシクロヘキサン（１０ｍｏｌ％、６ｍｇ、０．０５ｍｍｏｌ）および炭酸カリウム（１４５ｍｇ、１．０５ｍｍｏｌ）の１，４−ジオキサン（１ｍｌ）中混合物を、マイクロ波容器中１８０℃で４５分間撹拌した。反応混合物を冷却し、５ｇのプレパックシリカカラムに加え、ついで、酢酸エチルで溶出し、生成物を、さらにマス・ディレクテッド自動精製により精製して、標題化合物のクロップを淡ベージュ固体として得た（６５ｍｇ、３５％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３７４（ＥＳ＋）、保持時間３．５５分；Ｃ_１６Ｈ_１８Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値３７３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８５（４Ｈ，ｍ），２．７０（２Ｈ，ｍ），２．７４（６Ｈ，ｓ），２．７７（２Ｈ，ｍ），７．７２（２Ｈ，ｍ），７．８９（２Ｈ，ｍ） Example 7: N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide

4-iodo-N, N-dimethylbenzenesulfonamide (156 mg, 0.5 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (105 mg, 0.55 mmol), iodine 1,4-dioxane of copper (I) chloride (1 mol%, 1 mg, 0.005 mmol), trans-1,2-diaminocyclohexane (10 mol%, 6 mg, 0.05 mmol) and potassium carbonate (145 mg, 1.05 mmol) The mixture in (1 ml) was stirred in a microwave vessel at 180 ° C. for 45 minutes. The reaction mixture was cooled and added to a 5 g pre-packed silica column, then eluted with ethyl acetate and the product was further purified by mass directed auto-purification to give a crop of the title compound as a light beige solid ( 65 mg, 35%).
LC / Mass Spec (ES): Found 374 (ES +), retention time 3.55 _{min; C 16 H 18 F 3 N} 3 O 2 S Calculated 373
¹ H-NMR (400 MHz, CDCl ₃ ): 1.85 (4H, m), 2.70 (2H, m), 2.74 (6H, s), 2.77 (2H, m), 7.72 (2H, m), 7.89 (2H, m)

４−ヨウドアセトフェノンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例７に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３０９（ＥＳ＋）、保持時間３．５２分；Ｃ_１６Ｈ_１５Ｆ_３Ｎ_２Ｏとして計算値３０８
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８４（４Ｈ，ｍ），２．６４（３Ｈ，ｓ），２．７０（２Ｈ，ｍ），２．７７（２Ｈ，ｍ），７．６４（２Ｈ，ｍ），８．０７（２Ｈ，ｍ） Example 8: 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethanone

The title compound was prepared in a similar manner as described in Example 7 from 4-iodoacetophenone and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole.
LC / mass spectrum (ES): found 309 (ES +), retention time 3.52 minutes; calculated 308 as C ₁₆ H ₁₅ F ₃ N ₂ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.84 (4H, m), 2.64 (3H, s), 2.70 (2H, m), 2.77 (2H, m), 7.64 (2H, m), 8.07 (2H, m)

１−（４−ブロモフェニル）−１−プロパノンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例１に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３２３（ＥＳ＋）、保持時間３．７５分；Ｃ_１７Ｈ_１７Ｆ_３Ｎ_２Ｏとして計算値３２２
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．２５（３Ｈ，ｔ，Ｊ＝７Ｈｚ），１．８４（４Ｈ，ｍ），２．６９（２Ｈ，ｍ），２．７８（２Ｈ，ｍ），３．０４（２Ｈ，クォート，Ｊ＝７Ｈｚ），７．６３（２Ｈ，ｍ），８．０７（２Ｈ，ｍ） Example 9: 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone

In a manner analogous to that described in Example 1 from 1- (4-bromophenyl) -1-propanone and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole, the title The compound was prepared.
LC / Mass Spec (ES): Found 323 (ES +), retention time 3.75 _{min; C 17 H 17 F 3 N} 2 O Calculated 322
¹ H-NMR (400 MHz, CDCl ₃ ): 1.25 (3H, t, J = 7 Hz), 1.84 (4H, m), 2.69 (2H, m), 2.78 (2H, m) , 3.04 (2H, quote, J = 7Hz), 7.63 (2H, m), 8.07 (2H, m)

４−ブロモフェニルメチルスルホンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例７に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３４５（ＥＳ＋）、保持時間３．２６分；Ｃ_１５Ｈ_１５Ｆ_３Ｎ_２Ｏ_２Ｓとして計算値３４４
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８６（４Ｈ，ｍ），２．７０（２Ｈ，ｍ），２．８０（２Ｈ，ｍ），３．１０（３Ｈ，ｓ），７．７６（２Ｈ，ｍ），８．０６（２Ｈ，ｍ） Example 10: 1- [4- (methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

The title compound was prepared in a similar manner as described in Example 7 from 4-bromophenylmethylsulfone and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole.
LC / Mass Spec (ES): Found 345 (ES +), retention time 3.26 _{min; C 15 H 15 F 3 N} 2 O 2 Calculated S 344
¹ H-NMR (400 MHz, CDCl ₃ ): 1.86 (4H, m), 2.70 (2H, m), 2.80 (2H, m), 3.10 (3H, s), 7.76 (2H, m), 8.06 (2H, m)

４−ブロモフェニルアセトンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例７に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３２３（ＥＳ＋）、保持時間３．４４分；Ｃ_１７Ｈ_１７Ｆ_３Ｎ_２Ｏとして計算値３２２
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．１９（３Ｈ，ｓ），２．６９（４Ｈ，ｍ），３．７６（２Ｈ，ｓ），７．３０（２Ｈ，ｍ），７．４６（２Ｈ，ｍ） Example 11: 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone

The title compound was prepared in a similar manner as described in Example 7 from 4-bromophenylacetone and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole.
LC / Mass Spec (ES): Found 323 (ES +), retention time 3.44 _{min; C 17 H 17 F 3 N} 2 O Calculated 322
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.19 (3H, s), 2.69 (4H, m), 3.76 (2H, s), 7.30 (2H, m), 7.46 (2H, m)

２−（４−ブロモフェニル）−Ｎ，Ｎ−ジメチルアセトアミドおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例７に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３５２（ＥＳ＋）、保持時間３．１５分；Ｃ_１８Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３５１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８１（４Ｈ，ｍ），２．６９（４Ｈ，ｍ），２．９９（３Ｈ，ｓ），３．０２（３Ｈ，ｓ），３．７６（２Ｈ，ｓ），７．３５（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４３（２Ｈ，ｍ） Example 12: N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide

A method similar to that described in Example 7 from 2- (4-bromophenyl) -N, N-dimethylacetamide and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole. The title compound was prepared.
LC / mass spectrum (ES): found 352 (ES +), retention time 3.15 minutes; calculated 351 as C ₁₈ H ₂₀ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.81 (4H, m), 2.69 (4H, m), 2.99 (3H, s), 3.02 (3H, s), 3.76 (2H, s), 7.35 (2H, d, J = 8 Hz), 7.43 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸（１１３ｍｇ、０．３５ｍｍｏｌ）のジクロロメタン（４ｍｌ）中溶液を、Ｓａｒｓｔｅｄｔチューブ中で、固体１，１’−カルボニルジイミダゾール（６０ｍｇ、０．３７ｍｍｏｌ）で処理した。この混合物を室温にて３０分間振盪した。ジクロロメタン（２ｍｌ）中のピロリジン（３４ｍｇ、０．４８ｍｍｏｌ）を加え、振盪を室温にて１６時間続けた。反応混合物を飽和炭酸水素ナトリウム水溶液（４ｍｌ）およびブライン（２ｍｌ）の混合物で洗浄した。有機層を、２ｇのＳＣＸカラムに加え、酢酸エチル（２５ｍｌ）で溶出し、溶媒を減圧下で除去し、残渣マス・ディレクテッド自動精製により精製して、標題化合物を黄色油として得た（３０ｍｇ、２３％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３７８（ＥＳ＋）、保持時間３．２８分；Ｃ_２０Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３７７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８１（４Ｈ，ｍ），１．８８（２Ｈ，ｍ），１．９６（２Ｈ，ｍ），２．６９（４Ｈ，ｍ），３．４４（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．５０（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．７１（２Ｈ，ｓ），７．３８（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４３（２Ｈ，ｍ） Example 13: 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

A solution of {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid (113 mg, 0.35 mmol) in dichloromethane (4 ml) was added to Sarstedt. Treated with solid 1,1′-carbonyldiimidazole (60 mg, 0.37 mmol) in a tube. The mixture was shaken for 30 minutes at room temperature. Pyrrolidine (34 mg, 0.48 mmol) in dichloromethane (2 ml) was added and shaking was continued for 16 hours at room temperature. The reaction mixture was washed with a mixture of saturated aqueous sodium bicarbonate (4 ml) and brine (2 ml). The organic layer was added to a 2 g SCX column and eluted with ethyl acetate (25 ml), the solvent was removed under reduced pressure and purified by residue mass directed autopurification to give the title compound as a yellow oil (30 mg 23%).
LC / mass spectrum (ES): found 378 (ES +), retention time 3.28 minutes; calculated 377 as C ₂₀ H ₂₂ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.81 (4H, m), 1.88 (2H, m), 1.96 (2H, m), 2.69 (4H, m), 3.44 (2H, t, J = 7 Hz), 3.50 (2H, t, J = 7 Hz), 3.71 (2H, s), 7.38 (2H, d, J = 8 Hz), 7.43 (2H , M)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびＮ−エチルメチルアミンから、０−１００％ヘキサン中酢酸エチルで溶出するフラッシュカラムクロマトグラフィーにより精製すること以外は、実施例１３に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３６６（ＥＳ＋）、保持時間３．２８分；Ｃ_１９Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３６５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．１２（３Ｈ，ｍ），１．８２（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．９５および２．９７（３Ｈ，ｓ（回転異性体）），３．３４−３．４７（２Ｈ，ｍ（回転異性体）），３．７５（２Ｈ，ｍ），７．３６（２Ｈ，ｍ），７．４４（２Ｈ，ｄ，Ｊ＝８Ｈｚ） Example 14: N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide

{4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid and N-ethylmethylamine from 0-100% ethyl acetate in hexane The title compound was prepared using a method similar to that described in Example 13 except that purification by flash column chromatography eluting.
LC / mass spectrum (ES): found 366 (ES +), retention time 3.28 minutes; calculated as C ₁₉ H ₂₂ F ₃ N ₃ O 365
¹ H-NMR (400 MHz, CDCl ₃ ): 1.12 (3H, m), 1.82 (4H, m), 2.68 (4H, m), 2.95 and 2.97 (3H, s ( Rotamer)), 3.34-3.47 (2H, m (rotamer)), 3.75 (2H, m), 7.36 (2H, m), 7.44 (2H, d, J = 8Hz)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびＮ−メチルベンジルアミンから、０−６６％ヘキサン中酢酸エチルで溶出するフラッシュカラムクロマトグラフィーにより精製すること以外は、実施例１３に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４２８（ＥＳ＋）、保持時間３．５５分；Ｃ_２４Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値４２７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６９（４Ｈ，ｍ），２．９３および２．９９（３Ｈ，ｓ，（回転異性体）），３．７８および３．８２（２Ｈ，ｓ，（回転異性体）），４．５５および４．６２（２Ｈ，ｓ，（回転異性体）），７．１２−７．４６（９Ｈ，ｍ） Example 15: N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide

{4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid and N-methylbenzylamine from 0-66% ethyl acetate in hexane The title compound was prepared using a method similar to that described in Example 13 except that purification by flash column chromatography eluting.
LC / mass spectrum (ES): found 428 (ES +), retention time 3.55 minutes; calculated 427 as C ₂₄ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.69 (4H, m), 2.93 and 2.99 (3H, s, (rotamer)), 3. 78 and 3.82 (2H, s, (rotamers)), 4.55 and 4.62 (2H, s, (rotamers)), 7.12-7.46 (9H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびＮ−メチルブチルアミンから、０−６６％ヘキサン中酢酸エチルで溶出するフラッシュカラムクロマトグラフィーにより精製すること以外は、実施例１３に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３９４（ＥＳ＋）、保持時間３．６３分；Ｃ_２１Ｈ_２６Ｆ_３Ｎ_３Ｏとして計算値３９３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：０．９４（３Ｈ，ｍ），１．２４−１．３５（２Ｈ，ｍ），１．４７−１．５５（２Ｈ，ｍ），１．８２（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．９５および２．９７（３Ｈ，ｓ（回転異性体）），３．２８および３．３９（２Ｈ，ｍ（回転異性体）），３．７５（２Ｈ，ｍ），７．３６（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４３（２Ｈ，ｄ，Ｊ＝８Ｈｚ） Example 16: N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide

Elution with {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid and N-methylbutylamine with 0-66% ethyl acetate in hexane The title compound was prepared using a method similar to that described in Example 13 except that it was purified by flash column chromatography.
LC / mass spectrum (ES): found 394 (ES +), retention time 3.63 minutes; calculated 393 as C ₂₁ H ₂₆ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 0.94 (3H, m), 1.24-1.35 (2H, m), 1.47-1.55 (2H, m), 1.82 ( 4H, m), 2.68 (4H, m), 2.95 and 2.97 (3H, s (rotamers)), 3.28 and 3.39 (2H, m (rotamers)), 3.75 (2H, m), 7.36 (2H, d, J = 8 Hz), 7.43 (2H, d, J = 8 Hz)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびＮ−メチルフェネチルアミンから、０−８８％ヘキサン中酢酸エチルで溶出するフラッシュカラムクロマトグラフィー、ついで、マス・ディレクテッド自動精製により精製すること以外は、実施例１３に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４４２（ＥＳ＋）、保持時間３．５８分；Ｃ_２５Ｈ_２６Ｆ_３Ｎ_３Ｏとして計算値４４１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８１（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．８３（２Ｈ，ｍ），２．８９および３．０１（３Ｈ，ｓ（回転異性体）），３．４１および３．７３（２Ｈ，ｓ（回転異性体）），３．５４および３．６３（２Ｈ，ｔ，Ｊ＝７Ｈｚ（回転異性体）），７．１７（３Ｈ，ｍ），７．２９（４Ｈ，ｍ），７．４２（２Ｈ，ｍ） Example 17: N-methyl-N- (2-phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamide

Elution from {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid and N-methylphenethylamine with 0-88% ethyl acetate in hexane The title compound was prepared using a method similar to that described in Example 13 except that it was purified by flash column chromatography followed by mass directed automated purification.
LC / Mass Spec (ES): Found 442 (ES +), retention time 3.58 _{min; C 25 H 26 F 3 N} 3 O Calculated 441
¹ H-NMR (400 MHz, CDCl ₃ ): 1.81 (4H, m), 2.68 (4H, m), 2.83 (2H, m), 2.89 and 3.01 (3H, s ( Rotamers)), 3.41 and 3.73 (2H, s (rotamers)), 3.54 and 3.63 (2H, t, J = 7 Hz (rotamers)), 7.17 ( 3H, m), 7.29 (4H, m), 7.42 (2H, m)

１−｛［４−（ブロモメチル）フェニル］カルボニル｝ピロリジン（８４ｍｇ、０．３１ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（６０ｍｇ、０．３２ｍｍｏｌ）、および炭酸カリウム（８７ｍｇ、０．６３ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（２ｍｌ）中混合物を、マイクロ波反応器中１０分間１４０℃で撹拌した。反応混合物を冷却し、ジクロロメタンおよび水間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で最小容量にした。粗生成物をマス・ディレクテッド自動精製を用いて精製して、標題化合物を淡黄色油として得た（６３ｍｇ、５４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３７８（ＥＳ＋）、保持時間３．１１分；Ｃ_２０Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３７７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６９−１．８０（４Ｈ，ｍ），１．８７（２Ｈ，ｍ），１．９６（２Ｈ，ｍ），２．４３（２Ｈ，ｍ），２．６０（２Ｈ，ｍ），３．４０（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．６４（２Ｈ，ｔ，Ｊ＝７Ｈｚ），５．２７（２Ｈ，ｓ），７．１３（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４８（２Ｈ，ｄｄ，Ｊ＝６Ｈｚ，および２Ｈｚ） Example 18: 1-{[4- (1-pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

1-{[4- (Bromomethyl) phenyl] carbonyl} pyrrolidine (84 mg, 0.31 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (60 mg, 0.32 mmol) , And potassium carbonate (87 mg, 0.63 mmol) in N, N-dimethylformamide (2 ml) was stirred in a microwave reactor for 10 minutes at 140 ° C. The reaction mixture was cooled and partitioned between dichloromethane and water. The organic layer was dried over sodium sulfate and brought to a minimum volume under reduced pressure. The crude product was purified using mass directed automatic purification to give the title compound as a pale yellow oil (63 mg, 54%).
LC / Mass Spec (ES): Found 378 (ES +), retention time 3.11 _{min; C 20 H 22 F 3 N} 3 O Calculated 377
¹ H-NMR (400 MHz, CDCl ₃ ): 1.69-1.80 (4H, m), 1.87 (2H, m), 1.96 (2H, m), 2.43 (2H, m) , 2.60 (2H, m), 3.40 (2H, t, J = 7 Hz), 3.64 (2H, t, J = 7 Hz), 5.27 (2H, s), 7.13 (2H) , D, J = 8 Hz), 7.48 (2H, dd, J = 6 Hz, and 2 Hz)

１−［２−（４−ブロモフェニル）プロパノイル］ピロリジン（１４０ｍｇ、０．５ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（９５ｍｇ、０．５ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、１０ｍｇ、０．０５ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１０ｍｇ、０．１ｍｍｏｌ）および炭酸カリウム（１３８ｍｇ、１ｍｍｏｌ）のジメチルスルホキシド（２ｍｌ）中混合物を、マイクロ波容器中１９０℃で１．５時間撹拌した。反応混合物を冷却し、酢酸エチルおよび水間で分配した。有機層を硫酸ナトリウムで乾燥し、溶媒を減圧下で除去した。得られた生成物を、最初にジクロロメタン中の物質を、５ｇのプレパックシリカカラムに加えて酢酸エチルで溶出し、ついで、マス・ディレクテッド自動精製に付して精製して、標題化合物のクロップを褐色油として得た（８ｍｇ、４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３９２（ＥＳ＋）、保持時間３．４５分；Ｃ_２１Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値３９１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．４７（３Ｈ，ｄ，Ｊ＝７Ｈｚ），１．７４−１．９２（８Ｈ，ｍ），２．６９（４Ｈ，ｍ），３．１７（１Ｈ，ｍ），３．４０−３．５７（３Ｈ，ｍ），３．７９（１Ｈ，ｍ），７．４０（４Ｈ，ｍ） Example 19: 1- {4- [1-methyl-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazole

1- [2- (4-Bromophenyl) propanoyl] pyrrolidine (140 mg, 0.5 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (95 mg, 0.5 mmol) , Copper (I) iodide (10 mol%, 10 mg, 0.05 mmol), N, N-dimethylglycine (20 mol%, 10 mg, 0.1 mmol) and potassium carbonate (138 mg, 1 mmol) in dimethyl sulfoxide (2 ml) Was stirred in a microwave vessel at 190 ° C. for 1.5 hours. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure. The resulting product was first purified by subjecting the material in dichloromethane to a 5 g pre-packed silica column, eluting with ethyl acetate, and then subjected to mass directed autopurification to yield a crop of the title compound. Obtained as a brown oil (8 mg, 4%).
LC / mass spectrum (ES): found 392 (ES +), retention time 3.45 minutes; calculated 391 as C ₂₁ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.47 (3H, d, J = 7 Hz), 1.74-1.92 (8H, m), 2.69 (4H, m), 3.17 ( 1H, m), 3.40-3.57 (3H, m), 3.79 (1H, m), 7.40 (4H, m)

３−（４−ブロモフェニル）−Ｎ，Ｎ−ジメチルプロパンアミドおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例１に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３６６（ＥＳ＋）、保持時間３．２３分；Ｃ_１９Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３６５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６３（２Ｈ，ｔ，Ｊ＝８Ｈｚ），２．６７（４Ｈ，ｍ），２．９６（６Ｈ，ｓ），３．０２（２Ｈ，ｔ，Ｊ＝８Ｈｚ），７．３２（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．３９（２Ｈ，ｍ） Example 20: N, N-dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide

Similar to the method described in Example 1 from 3- (4-bromophenyl) -N, N-dimethylpropanamide and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole. The title compound was prepared by the method.
LC / mass spectrum (ES): found 366 (ES +), retention time 3.23 minutes; calculated as C ₁₉ H ₂₂ F ₃ N ₃ O 365
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.63 (2H, t, J = 8 Hz), 2.67 (4H, m), 2.96 (6H, s) 3.02 (2H, t, J = 8 Hz), 7.32 (2H, d, J = 8 Hz), 7.39 (2H, m)

１−［３−（４−ブロモフェニル）プロパノイル］ピロリジンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例１９に記載の方法と同様の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３９２（ＥＳ＋）、保持時間３．４０分；Ｃ_２１Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値３９１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８１（４Ｈ，ｍ），１．８５（２Ｈ，ｍ），１．９２（２Ｈ，ｍ），２．５８（２Ｈ，ｍ），２．６４（４Ｈ，ｍ），３．０４（２Ｈ，ｔ，Ｊ＝８Ｈｚ），３．３３（２Ｈ，ｔ，Ｊ＝７Ｈｚ），３．４７（２Ｈ，ｔ，Ｊ＝７Ｈｚ），７．３２（２Ｈ，ｍ），７．３９（２Ｈ，ｍ） Example 21: 1- {4- [3-oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

A method similar to that described in Example 19 was prepared from 1- [3- (4-bromophenyl) propanoyl] pyrrolidine and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole. Used to prepare the title compound.
LC / mass spectrum (ES): found 392 (ES +), retention time 3.40 minutes; calculated 391 as C ₂₁ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.81 (4H, m), 1.85 (2H, m), 1.92 (2H, m), 2.58 (2H, m), 2.64 (4H, m), 3.04 (2H, t, J = 8 Hz), 3.33 (2H, t, J = 7 Hz), 3.47 (2H, t, J = 7 Hz), 7.32 (2H , M), 7.39 (2H, m)

１−｛［１−（４−ヨウドフェニル）シクロプロピル］カルボニル｝ピロリジンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例１９に記載の方法と同様の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４０４（ＥＳ＋）、保持時間３．４３分；Ｃ_２２Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値４０３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．１８（２Ｈ，ｍ），１．４８（２Ｈ，ｍ），１．７５−１．８３（８Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．１９（２Ｈ，ｍ），３．４９（２Ｈ，ｍ），７．２８（２Ｈ，ｍ），７．４１（２Ｈ，ｍ） Example 22: 1- {4- [1- (1-pyrrolidinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

From 1-{[1- (4-iodophenyl) cyclopropyl] carbonyl} pyrrolidine and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole, the method described in Example 19 and A similar method was used to prepare the title compound.
LC / mass spectrum (ES): found 404 (ES +), retention time 3.43 minutes; calculated 403 as C ₂₂ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.18 (2H, m), 1.48 (2H, m), 1.75-1.83 (8H, m), 2.68 (4H, m) 3.19 (2H, m), 3.49 (2H, m), 7.28 (2H, m), 7.41 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびピペリジンから、実施例２に記載の方法と類似の方法を用いて、標題化合物を調製し、さらにマス・ディレクテッド自動精製により精製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３９２（ＥＳ＋）、保持時間３．４５分；Ｃ_２１Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値３９１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．４１（２Ｈ，ｍ），１．５３（２Ｈ，ｍ），１．５９（２Ｈ，ｍ），１．８２（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．３９（２Ｈ，ｍ），３．５８（２Ｈ，ｍ），３．７７（２Ｈ，ｓ），７．３６（２Ｈ，ｍ），７．４４（２Ｈ，ｍ） Example 23: 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

A method similar to that described in Example 2 was used from {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid and piperidine. The title compound was prepared and further purified by mass directed automated purification.
LC / mass spectrum (ES): found 392 (ES +), retention time 3.45 minutes; calculated 391 as C ₂₁ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.41 (2H, m), 1.53 (2H, m), 1.59 (2H, m), 1.82 (4H, m), 2.68 (4H, m), 3.39 (2H, m), 3.58 (2H, m), 3.77 (2H, s), 7.36 (2H, m), 7.44 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸（６５ｍｇ、０．２ｍｍｏｌ）のジクロロメタン（２ｍｌ）中溶液を、固体１，１’−カルボニルジイミダゾール（３３ｍｇ、０．２ｍｍｏｌ）で処理した。この混合物を室温で１５分間撹拌した。３，３−ジフルオロピロリジン塩酸塩（２９ｍｇ、０．２ｍｍｏｌ）、ついで、トリエチルアミン（２１ｍｇ、０．２１ｍｍｏｌ）を加え、室温にて１時間撹拌を続けた。反応混合物を減圧下で最小容量にし、ついで、マス・ディレクテッド自動精製により精製して、標題化合物を黄色油として得た（５３ｍｇ、６４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値４１４（ＥＳ＋）、保持時間３．３４分；Ｃ_２０Ｈ_２０Ｆ_５Ｎ_３Ｏとして計算値４１３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．３５（１Ｈ，ｍ），２．４３（１Ｈ，ｍ），２．６９（４Ｈ，ｍ），３．６７−３．８７（６Ｈ，ｍ），７．３６（２Ｈ，ｍ），７．４６（２Ｈ，ｍ） Example 24: 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazole

A solution of {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid (65 mg, 0.2 mmol) in dichloromethane (2 ml) was added to a solid Treated with 1,1′-carbonyldiimidazole (33 mg, 0.2 mmol). The mixture was stirred at room temperature for 15 minutes. 3,3-Difluoropyrrolidine hydrochloride (29 mg, 0.2 mmol) was added followed by triethylamine (21 mg, 0.21 mmol) and stirring was continued at room temperature for 1 hour. The reaction mixture was brought to minimum volume under reduced pressure and then purified by mass directed auto-purification to give the title compound as a yellow oil (53 mg, 64%).
LC / Mass Spec (ES): Found 414 (ES +), retention time 3.34 _{min; C 20 H 20 F 5 N} 3 O Calculated 413
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.35 (1H, m), 2.43 (1H, m), 2.69 (4H, m), 3.67 -3.87 (6H, m), 7.36 (2H, m), 7.46 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびＮ−メチルプロピルアミンから、実施例２に記載の方法と類似の方法を用いて、標題化合物を調製し、さらにマス・ディレクテッド自動精製により精製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３８０（ＥＳ＋）、保持時間３．４１分；Ｃ_２０Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値３７９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：０．８９（３Ｈ，ｍ），１．５６（２Ｈ，ｍ），１．８１（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．９６（３Ｈ，ｍ），３．２６（１Ｈ，ｍ），３．３６（１Ｈ，ｍ），３．７６（２Ｈ，ｍ），７．３６（２Ｈ，ｄ，Ｊ＝９Ｈｚ），７．４４（２Ｈ，ｄ，Ｊ＝８Ｈｚ） Example 25: N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide

Similar to the method described in Example 2 from {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid and N-methylpropylamine. The title compound was prepared using the procedure described above and further purified by mass directed automated purification.
LC / mass spectrum (ES): Found 380 (ES +), retention time 3.41 min; calculated as 379 as C ₂₀ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 0.89 (3H, m), 1.56 (2H, m), 1.81 (4H, m), 2.68 (4H, m), 2.96 (3H, m), 3.26 (1H, m), 3.36 (1H, m), 3.76 (2H, m), 7.36 (2H, d, J = 9 Hz), 7.44 ( 2H, d, J = 8Hz)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸およびシクロペンチルアミンから、マス・ディレクテッド自動精製により精製すること以外は実施例２に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３９２（ＥＳ＋）、保持時間３．３７分；Ｃ_２１Ｈ_２４Ｆ_３Ｎ_３Ｏとして計算値３９１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．２６（２Ｈ，ｍ），１．５３−１．６３（４Ｈ，ｍ），１．８２（４Ｈ，ｍ），１．９２−２．００（２Ｈ，ｍ），２．７０（４Ｈ，ｍ），３．５８（２Ｈ，ｓ），４．２０（１Ｈ，ｍ），５．２９（１Ｈ，ｍ），７．３６（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４８（２Ｈ，ｍ） Example 26: N-cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide

{4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} Acetic acid and cyclopentylamine, except for purification by mass directed automatic purification The title compound was prepared using a method similar to that described in Example 2.
LC / mass spectrum (ES): found 392 (ES +), retention time 3.37 minutes; calculated 391 as C ₂₁ H ₂₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.26 (2H, m), 1.53-1.63 (4H, m), 1.82 (4H, m), 1.92-2.00 ( 2H, m), 2.70 (4H, m), 3.58 (2H, s), 4.20 (1H, m), 5.29 (1H, m), 7.36 (2H, d, J = 8 Hz), 7.48 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸（６５ｍｇ、０．２ｍｍｏｌ）のジクロロメタン（２ｍｌ）中溶液を、固体１，１’−カルボニルジイミダゾール（３３ｇ、０．２ｍｍｏｌ）で処理した。この混合物を室温にて１５分間振盪した。メチルチオフェン−２−イルメチルアミン（２５ｍｇ、０．２ｍｍｏｌ）を加え、振盪を室温にて１時間続けた。反応混合物をジクロロメタンおよび飽和炭酸水素ナトリウム水溶液（３ｍｌ）間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、黄色油を得、これをマス・ディレクテッド自動精製を用いて精製して、標題化合物を黄色油として得た（４２ｍｇ、４８％）。
ＬＣ／マススペクトル（ＥＳ）：実測値４３４（ＥＳ＋）、保持時間３．５４分；Ｃ_２２Ｈ_２２Ｆ_３Ｎ_３ＯＳとして計算値４３３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６９（４Ｈ，ｍ），２．９７および３．０１（３Ｈ，ｓ（回転異性体）），３．７９および３．８６（２Ｈ，ｓ，（回転異性体）），４．６６および４．７４（２Ｈ，ｓ（回転異性体）），６．８９−６．９９（２Ｈ，ｍ），７．２３（１Ｈ，ｍ），７．３６（２Ｈ，ｍ），７．４４（２Ｈ，ｍ） Example 27: N-methyl-N- (2-thienylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamide

A solution of {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid (65 mg, 0.2 mmol) in dichloromethane (2 ml) was added to a solid Treated with 1,1′-carbonyldiimidazole (33 g, 0.2 mmol). The mixture was shaken for 15 minutes at room temperature. Methylthiophen-2-ylmethylamine (25 mg, 0.2 mmol) was added and shaking was continued for 1 hour at room temperature. The reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate (3 ml). The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give a yellow oil, which was purified using mass directed automatic purification to give the title compound as a yellow oil (42 mg, 48%). .
LC / mass spectrum (ES): found 434 (ES +), retention time 3.54 minutes; calculated 433 as C ₂₂ H ₂₂ F ₃ N ₃ OS
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.69 (4H, m), 2.97 and 3.01 (3H, s (rotamers)), 3.79. And 3.86 (2H, s, (rotamers)), 4.66 and 4.74 (2H, s (rotamers)), 6.89-6.99 (2H, m), 7.23. (1H, m), 7.36 (2H, m), 7.44 (2H, m)

（４−ブロモフェニル）アセトニトリルおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例７に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３０６（ＥＳ＋）、保持時間３．３４分；Ｃ_１６Ｈ_１４Ｆ_３Ｎ_３として計算値３０５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），３．８２（２Ｈ，ｓ），７．４４（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．５３（２Ｈ，ｍ） Example 28: {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile

The title compound was prepared in a manner analogous to that described in Example 7 from (4-bromophenyl) acetonitrile and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole.
LC / mass spectrum (ES): found 306 (ES +), retention time 3.34 minutes; calculated as 305 for C ₁₆ H ₁₄ F ₃ N ₃
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.70 (4H, m), 3.82 (2H, s), 7.44 (2H, d, J = 8 Hz) 7.53 (2H, m)

４−ヨウドベンジルアルコール（１．２３ｇ、５．２５ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（９５０ｍｇ、５ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、９５ｍｇ、０．５ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１０３ｍｇ、１ｍｍｏｌ）および炭酸カリウム（１．４５ｇ、１０．５ｍｍｏｌ）のジメチルスルホキシド（３０ｍｌ）中混合物を、油浴中１３０℃で２３時間撹拌した。反応混合物を冷却し、ジクロロメタン（３０ｍｌ）およびブライン（１５０ｍｌ）間で分配した。有機層を濾過により除去し、溶媒を減圧下で除去した。得られた生成物を、０−６０％ペンタン中酢酸エチルで溶出するＢｉｏｔａｇｅ４０＋Ｍカラムのフラッシュカラムクロマトグラフィーにより精製して、標題化合物を黄色油として得た（１．２７ｇ、８６％）。
ＬＣ／マススペクトル（ＥＳ）：実測値２９７（ＥＳ＋）、保持時間３．０６分；Ｃ_１５Ｈ_１５Ｆ_３Ｎ_２Ｏとして計算値２９６
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７６（１Ｈ，ｔ，Ｊ＝６Ｈｚ），１．８２（４Ｈ，ｍ），２．６９（４Ｈ，ｍ），４．７７（２Ｈ，ｍ），７．４８（４Ｈ，ｍ） Example 29: {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanol

4-iodobenzyl alcohol (1.23 g, 5.25 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (950 mg, 5 mmol), copper (I) iodide (10 mol) %, 95 mg, 0.5 mmol), N, N-dimethylglycine (20 mol%, 103 mg, 1 mmol) and potassium carbonate (1.45 g, 10.5 mmol) in dimethyl sulfoxide (30 ml) in an oil bath at 130 ° C. For 23 hours. The reaction mixture was cooled and partitioned between dichloromethane (30 ml) and brine (150 ml). The organic layer was removed by filtration and the solvent was removed under reduced pressure. The resulting product was purified by flash column chromatography on a Biotage 40 + M column eluting with 0-60% ethyl acetate in pentane to give the title compound as a yellow oil (1.27 g, 86%).
LC / Mass Spec (ES): Found 297 (ES +), retention time 3.06 _{min; C 15 H 15 F 3 N} 2 O Calculated 296
¹ H-NMR (400 MHz, CDCl ₃ ): 1.76 (1H, t, J = 6 Hz), 1.82 (4H, m), 2.69 (4H, m), 4.77 (2H, m) , 7.48 (4H, m)

Ｎ−［（４−ブロモフェニル）メチル］−Ｎ−メチルアセトアミドおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例１に記載の方法と類似の方法で、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３５２（ＥＳ＋）、保持時間３．１３分；Ｃ_１８Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３５１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．１８（３Ｈ，ｍ），２．６６（４Ｈ，ｍ），２．９４および２．９６（３Ｈ，ｓ（回転異性体）），４．５８および４．６３（２Ｈ，ｓ（回転異性体）），７．２６−７．３５（２Ｈ，ｍ（回転異性体），７．４２−７．５２（２Ｈ，ｍ（回転異性体）） Example 30: N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide

Similar to the method described in Example 1 from N-[(4-bromophenyl) methyl] -N-methylacetamide and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole. The title compound was prepared by the method.
LC / mass spectrum (ES): found 352 (ES +), retention time 3.13 minutes; calculated 351 as C ₁₈ H ₂₀ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.18 (3H, m), 2.66 (4H, m), 2.94 and 2.96 (3H, s ( Rotamers)), 4.58 and 4.63 (2H, s (rotamers)), 7.26-7.35 (2H, m (rotamers), 7.42-7.52 (2H , M (rotamers))

１−［（４−ヨウドフェニル）メチル］−２−ピロリジノンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例１９に記載の方法と同様の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３６４（ＥＳ＋）、保持時間３．１８分；Ｃ_１９Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３６３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．０２（２Ｈ，ｍ），２．４５（２Ｈ，ｍ），２．６９（４Ｈ，ｍ），３．２６（２Ｈ，ｍ），４．５０（２Ｈ，ｍ），７．３４（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４５（２Ｈ，ｍ） Example 31: 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone

Similar method to that described in Example 19 from 1-[(4-iodophenyl) methyl] -2-pyrrolidinone and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole Was used to prepare the title compound.
LC / mass spectrum (ES): found 364 (ES +), retention time 3.18 minutes; calculated as C ₁₉ H ₂₀ F ₃ N ₃ O 363
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.02 (2H, m), 2.45 (2H, m), 2.69 (4H, m), 3.26 (2H, m), 4.50 (2H, m), 7.34 (2H, d, J = 8 Hz), 7.45 (2H, m)

１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールおよびＮ−メチルプロパンアミドから、記載例１５に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３６６（ＥＳ＋）、保持時間３．３０分；Ｃ_１９Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３６５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．２０（３Ｈ，ｍ），１．８０（４Ｈ，ｍ），２．４１（２Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．９３および２．９７（３Ｈ，ｓ（回転異性体）），４．５８および４．６４（２Ｈ，ｓ（回転異性体）），７．２５−７．３５（２Ｈ，ｍ），７．４２−７．５１（２Ｈ，ｍ） Example 32: N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide

Similar to the method described in Description 15 from 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and N-methylpropanamide Was used to prepare the title compound.
LC / mass spectrum (ES): found 366 (ES +), retention time 3.30 minutes; calculated as C ₁₉ H ₂₂ F ₃ N ₃ O 365
¹ H-NMR (400 MHz, CDCl ₃ ): 1.20 (3H, m), 1.80 (4H, m), 2.41 (2H, m), 2.68 (4H, m), 2.93 And 2.97 (3H, s (rotamers)), 4.58 and 4.64 (2H, s (rotamers)), 7.25-7.35 (2H, m), 7.42- 7.51 (2H, m)

１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールおよびＮ−エチルアセトアミドから、記載例１５に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３６６（ＥＳ＋）、保持時間３．２８分；Ｃ_１９Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３６５
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．１４（３Ｈ，ｍ），１．８２（４Ｈ，ｍ），２．１２および２．２０（３Ｈ，ｓ（回転異性体）），２．６８（４Ｈ，ｍ），３．２９および３．４４（２Ｈ，クォート，Ｊ＝７Ｈｚ（回転異性体）），４．５７および４．６３（２Ｈ，ｓ，（回転異性体）），７．２９および７．３４（２Ｈ，ｄ，Ｊ＝８Ｈｚ（回転異性体）），７．４２および７．５０（２Ｈ，ｄ，Ｊ＝８Ｈｚ（回転異性体）） Example 33: N-ethyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide

Similar to the method described in Description Example 15 from 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and N-ethylacetamide. The title compound was prepared using the method.
LC / mass spectrum (ES): found 366 (ES +), retention time 3.28 minutes; calculated as C ₁₉ H ₂₂ F ₃ N ₃ O 365
¹ H-NMR (400 MHz, CDCl ₃ ): 1.14 (3H, m), 1.82 (4H, m), 2.12 and 2.20 (3H, s (rotamers)), 2.68. (4H, m), 3.29 and 3.44 (2H, quarts, J = 7 Hz (rotamers)), 4.57 and 4.63 (2H, s, (rotamers)), 7.29 And 7.34 (2H, d, J = 8 Hz (rotamers)), 7.42 and 7.50 (2H, d, J = 8 Hz (rotamers))

１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールおよび２−ピペリジノンから、記載例１５に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３７８（ＥＳ＋）、保持時間３．２９分；Ｃ_２０Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値３７７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７９（８Ｈ，ｍ），２．４８（２Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．２０（２Ｈ，ｍ），４．６４（２Ｈ，ｓ），７．３６（２Ｈ，ｄ，Ｊ＝８Ｈｚ），７．４３（２Ｈ，ｍ） Example 34: 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone

A method analogous to that described in Description 15 from 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and 2-piperidinone Was used to prepare the title compound.
LC / mass spectrum (ES): found 378 (ES +), retention time 3.29 min; calculated as C ₂₀ H ₂₂ F ₃ N ₃ O 377
¹ H-NMR (400 MHz, CDCl ₃ ): 1.79 (8H, m), 2.48 (2H, m), 2.68 (4H, m), 3.20 (2H, m), 4.64 (2H, s), 7.36 (2H, d, J = 8 Hz), 7.43 (2H, m)

５−（４−ブロモフェニル）−１−メチル−２−ピロリジノン（１４１ｍｇ、０．５６ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１１１ｍｇ、０．５８ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、１１ｍｇ、０．０６ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１２ｍｇ、０．１２ｍｍｏｌ）および炭酸カリウム（１６２ｍｇ、１．１７ｍｍｏｌ）のジメチルスルホキシド（３ｍｌ）中溶液を、マイクロ波容器中１８０℃で合計２時間撹拌した。反応混合物を、ジクロロメタン（２０ｍｌ）で洗浄する５ｇのプレパックシリカカラムにより濾過し、濾液を水（５０ｍｌ）で洗浄し、有機層を硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去し、試料をマス・ディレクテッド自動精製により精製した。最終生成物をジクロロメタン（３ｍｌ）および水（３ｍｌ）間で分配した。有機層を分離し、溶媒をロータリーエバポレーションにより除去して、標題化合物を褐色油として得た（１４ｍｇ、７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３６４（ＥＳ＋）、保持時間３．１４分；Ｃ_１９Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３６３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８８（５Ｈ，ｍ），２．４４−２．６５（３Ｈ，ｍ），２．７１（７Ｈ，ｍ），４．５８（１Ｈ，ｍ），７．３０（２Ｈ，ｍ），７．５２（２Ｈ，ｍ） Example 35: 1-methyl-5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone

5- (4-Bromophenyl) -1-methyl-2-pyrrolidinone (141 mg, 0.56 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (111 mg, 0. 58 mmol), copper (I) iodide (10 mol%, 11 mg, 0.06 mmol), N, N-dimethylglycine (20 mol%, 12 mg, 0.12 mmol) and potassium carbonate (162 mg, 1.17 mmol) in dimethylsulfoxide ( 3 ml) was stirred in a microwave vessel at 180 ° C. for a total of 2 hours. The reaction mixture was filtered through a 5 g pre-packed silica column washed with dichloromethane (20 ml), the filtrate was washed with water (50 ml) and the organic layer was dried over sodium sulfate. The solvent was removed by rotary evaporation and the sample was purified by mass directed auto purification. The final product was partitioned between dichloromethane (3 ml) and water (3 ml). The organic layer was separated and the solvent removed by rotary evaporation to give the title compound as a brown oil (14 mg, 7%).
LC / mass spectrum (ES): found 364 (ES +), retention time 3.14 minutes; calculated as C ₁₉ H ₂₀ F ₃ N ₃ O 363
¹ H-NMR (400 MHz, CDCl ₃ ): 1.88 (5H, m), 2.44-2.65 (3H, m), 2.71 (7H, m), 4.58 (1H, m) 7.30 (2H, m), 7.52 (2H, m)

典型的プロシージャ：ポリマー支持１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド（０．１ｍｍｏｌ、０．０６８ｇ、１．４２ｍｍｏｌ／ｇ）に、１−ヒドロキシ−７−アザベンゾトリアゾールの溶液（０．０１ｍｍｏｌ、０．８ｍｌ（テトラヒドロフラン：ジクロロメタン１：１））、ついで、４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（０．０１ｇ、０．０５ｍｍｏｌ）の１：３ Ｎ−メチル−２−ピロリジノン：テトラヒドロフラン中溶液、ついで、ジクロロメタン（０．２５ｍｌ）中のアミン（０．０５ｍｍｏｌ）を加えた。反応物を６０時間混合した。ついで、これにポリマー支持イソシアネート（０．０６８ｇ、０．１ｍｍｏｌ、１．５ｍｍｏｌ／ｇ）およびポリマー支持カルボネート（０．０６８ｇ、０．１ｍｍｏｌ、１．５ｍｍｏｌ／ｇ）を加え、さらに２４時間撹拌した。反応混合物を濾過し、溶媒をＧｅｎｅｖａｃで除去した。すべての生成物をさらにマス・ディレクテッド自動精製により精製した。

Examples 36-44:

Typical procedure: Polymer supported 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (0.1 mmol, 0.068 g, 1.42 mmol / g) in 1-hydroxy-7-azabenzotriazole solution (0 .01 mmol, 0.8 ml (tetrahydrofuran: dichloromethane 1: 1)) followed by 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid ( 0.01 g, 0.05 mmol) in 1: 3 N-methyl-2-pyrrolidinone: tetrahydrofuran followed by amine (0.05 mmol) in dichloromethane (0.25 ml). The reaction was mixed for 60 hours. Next, polymer-supported isocyanate (0.068 g, 0.1 mmol, 1.5 mmol / g) and polymer-supported carbonate (0.068 g, 0.1 mmol, 1.5 mmol / g) were added thereto, and the mixture was further stirred for 24 hours. The reaction mixture was filtered and the solvent was removed with Genevac. All products were further purified by mass directed automated purification.

４−［（４−ヨウドフェニル）カルボニル］モルホリン（１．９０ｇ、６．０ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１．１４ｇ、６．０ｍｍｏｌ）、酸化銅（Ｉ）（１０ｍｏｌ％、０．６ｍｍｏｌ、８６ｍｇ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１．２ｍｍｏｌ、１２４ｍｇ）、および炭酸セシウム（１２．０ｍｍｏｌ、３．９１ｇ）のジメチルスルホキシド（１６ｍｌ）中混合物を、１３０℃に加熱した油浴中アルゴン雰囲気下で２４時間加熱し、ついで、室温に冷却した。反応混合物をジクロロメタン（３０ｍｌ）および水（３０ｍｌ）間で分配した。有機層を分離し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去して、暗褐色残渣を得、これを、２０ｇのプレパックＩｓｏｌｕｔｅシリカカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物を褐色ガムとして得た（１．８６ｇ、８２％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３８０（ＥＳ＋）、保持時間３．０７分；Ｃ_１９Ｈ_２０Ｆ_３Ｎ_３Ｏ_２として計算値３７９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８４（４Ｈ，ｍ），２．７１（４Ｈ，ｍ），３．３６−３．９０（８Ｈ，ｍ），７．５３（２Ｈ，ｍ），７．５８（２Ｈ，ｍ） Example 45: 1- [4- (4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

4-[(4-iodophenyl) carbonyl] morpholine (1.90 g, 6.0 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (1.14 g, 6. 0 mmol), copper (I) oxide (10 mol%, 0.6 mmol, 86 mg), N, N-dimethylglycine (20 mol%, 1.2 mmol, 124 mg), and dimethyl cesium carbonate (12.0 mmol, 3.91 g) The mixture in sulfoxide (16 ml) was heated in an oil bath heated to 130 ° C. under an argon atmosphere for 24 hours and then cooled to room temperature. The reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml). The organic layer was separated and dried over sodium sulfate. Solvent was removed by rotary evaporation to give a dark brown residue which was added to a 20 g pre-packed Isolute silica column and eluted with 0-50% ethyl acetate in petroleum ether to give the title compound as a brown gum. (1.86 g, 82%).
LC / Mass Spec (ES): Found 380 (ES +), retention time 3.07 _{min; C 19 H 20 F 3 N} 3 O 2 Calculated 379
¹ H-NMR (400 MHz, CDCl ₃ ): 1.84 (4H, m), 2.71 (4H, m), 3.36-3.90 (8H, m), 7.53 (2H, m) 7.58 (2H, m)

（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）アミン（１．５６３ｇ、５．２９ｍｍｏｌ）、トリエチルアミン（１．４８ｍｌ、１０．５８ｍｍｏｌ）のジクロロメタン（４０ｍｌ）中溶液を、アルゴン雰囲気下氷浴中で撹拌した。メタンスルホニルクロライド（１．２１３ｇ、０．８２ｍｌ、１０．５８ｍｍｏｌ）を撹拌しながら滴下した。得られた混合物を室温にて５時間撹拌した。ついで、反応混合物をジクロロメタンおよび水間で分配した。有機層を分離し、硫酸ナトリウムで乾燥した。所望の生成物を、１０〜７０％ｎ−ペンタン中酢酸エチルを用いるシリカのカラムクロマトグラフィーにより単離して、ｎ−ペンタンでトリチュレートして、標題化合物を白色固体として得た（１．６０２ｇ、８１％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３７４（ＥＳ＋）、保持時間３．１２分；Ｃ_１６Ｈ_１８Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値３７３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），２．９２（３Ｈ，ｓ），４．３８（２Ｈ，ｄ，Ｊ＝６Ｈｚ），４．７０（１Ｈ，ｍ），７．４３−７．５４（４Ｈ，ｍ） Example 46: N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide

({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine (1.563 g, 5.29 mmol), triethylamine (1. A solution of 48 ml, 10.58 mmol) in dichloromethane (40 ml) was stirred in an ice bath under an argon atmosphere. Methanesulfonyl chloride (1.213 g, 0.82 ml, 10.58 mmol) was added dropwise with stirring. The resulting mixture was stirred at room temperature for 5 hours. The reaction mixture was then partitioned between dichloromethane and water. The organic layer was separated and dried over sodium sulfate. The desired product was isolated by column chromatography on silica using 10-70% ethyl acetate in n-pentane and triturated with n-pentane to give the title compound as a white solid (1.602 g, 81 %).
LC / mass spectrum (ES): found 374 (ES +), retention time 3.12 minutes; calculated 373 as C ₁₆ H ₁₈ F ₃ N ₃ O ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.68 (4H, m), 2.92 (3H, s), 4.38 (2H, d, J = 6 Hz) , 4.70 (1H, m), 7.43-7.54 (4H, m)

リチウムジイソプロピルアミド（ＴＨＦ中２Ｍ、０．５ｍｌ）のＴＨＦ（５ｍｌ）中溶液を、ＣＯ_２／メタノール浴中、アルゴン雰囲気下で撹拌しながら−７８℃に冷却した。１−｛４−［２−オキソ−２−（１−ピロリジニル）エチル］フェニル｝−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１５０ｍｇ、０．４ｍｍｏｌ）のＴＨＦ（０．５ｍｌ）中溶液を、アルゴン雰囲気下で滴下した。得られた混合物を１時間−７８℃で撹拌した。ついで、２−フルオロ−３，３−ジメチル−２，３−ジヒドロ−１，２−ベンズイソチアゾール１，１−ジオキシド（１８９ｍｇ、０．８８ｍｍｏｌ）のＴＨＦ（５ｍｌ）中溶液を加えた。得られた混合物を−７８℃で１時間撹拌し、ゆっくりと室温に加温した。反応混合物を、飽和塩化アンモニウム水溶液でクエンチし、酢酸エチルおよび飽和塩化アンモニウム水溶液間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、褐色油を得（２６０ｍｇ）、これをマス・ディレクテッド自動精製により精製して、モノ（実施例４７）およびビス（実施例４８）フッ素化生成物を得た。

Examples 47-48:

A solution of lithium diisopropylamide (2M in THF, 0.5 ml) in THF (5 ml) was cooled to −78 ° C. with stirring in a CO ₂ / methanol bath under an argon atmosphere. 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (150 mg, 0.4 mmol) Of THF in 0.5 ml was added dropwise under an argon atmosphere. The resulting mixture was stirred at −78 ° C. for 1 hour. A solution of 2-fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (189 mg, 0.88 mmol) in THF (5 ml) was then added. The resulting mixture was stirred at −78 ° C. for 1 hour and slowly warmed to room temperature. The reaction mixture was quenched with saturated aqueous ammonium chloride and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give a brown oil (260 mg), which was purified by mass directed auto-purification to give mono (Example 47) and bis (Example 48) A fluorinated product was obtained.

１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールおよびＮ−メチルメタンスルホンアミドから、記載例１５に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値３８８（ＥＳ＋）、保持時間３．３５分；Ｃ_１７Ｈ_２０Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値３８７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），２．７９（３Ｈ，ｓ），２．８８（３Ｈ，ｓ），４．３６（２Ｈ，ｓ），７．４８（４Ｈ，ｍ） Example 49: N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide

From 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and N-methylmethanesulfonamide, the method of Description 15 A similar method was used to prepare the title compound.
LC / mass spectrum (ES): found 388 (ES +), retention time 3.35 minutes; calculated as C ₁₇ H ₂₀ F ₃ N ₃ O ₂ S 387
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.70 (4H, m), 2.79 (3H, s), 2.88 (3H, s), 4.36 (2H, s), 7.48 (4H, m)

４−｛［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］メチル｝アニリン（１６６ｍｇ、０．５６ｍｍｏｌ）のジクロロメタン（４ｍｌ）中溶液を、ジイソプロピルエチルアミン（１．１２ｍｍｏｌ、１４６ｍｇ）、ついで、４−クロロブチリルクロライド（８０ｍｇ、０．５６ｍｍｏｌ）で処理した。室温にて１５分間撹拌した後、水素化ナトリウム（鉱油中６０％）（２２ｍｇ、０．５５ｍｍｏｌ）の懸濁液を加え、撹拌を３０分間加えた。ジクロロメタンをエアーブローにより除去し、ジメチルホルムアミド（３ｍｌ）を加え、撹拌を３０分間続けた。反応混合物を、ジクロロメタンおよび水（２×５ｍｌ）間で分配した。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸発させて、黄色油を得（１９０ｍｇ）、マス・ディレクテッド自動精製により精製して、標題化合物を黄色油として得た（３９ｍｇ、１９％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３６４（ＥＳ＋）、保持時間３．１３分；Ｃ_１９Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３６３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６５−１．８１（４Ｈ，ｍ），２．１５（２Ｈ，ｍ），２．４３（２Ｈ，ｍ），２．６２（４Ｈ，ｍ），３．８４（２Ｈ，ｍ），５．２２（２Ｈ，ｓ），７．１５（２Ｈ，ｄ，Ｊ＝９Ｈｚ），７．５７（２Ｈ，ｍ） Example 50: 1- (4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl} phenyl) -2-pyrrolidinone

A solution of 4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl} aniline (166 mg, 0.56 mmol) in dichloromethane (4 ml) was diluted with diisopropyl Treated with ethylamine (1.12 mmol, 146 mg) followed by 4-chlorobutyryl chloride (80 mg, 0.56 mmol). After stirring at room temperature for 15 minutes, a suspension of sodium hydride (60% in mineral oil) (22 mg, 0.55 mmol) was added and stirring was added for 30 minutes. Dichloromethane was removed by air blow, dimethylformamide (3 ml) was added and stirring was continued for 30 minutes. The reaction mixture was partitioned between dichloromethane and water (2 × 5 ml). The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give a yellow oil (190 mg) which was purified by mass directed auto-purification to give the title compound as a yellow oil (39 mg, 19%).
LC / mass spectrum (ES): found 364 (ES +), retention time 3.13 minutes; calculated as C ₁₉ H ₂₀ F ₃ N ₃ O 363
¹ H-NMR (400 MHz, CDCl ₃ ): 1.65 to 1.81 (4H, m), 2.15 (2H, m), 2.43 (2H, m), 2.62 (4H, m) 3.84 (2H, m), 5.22 (2H, s), 7.15 (2H, d, J = 9 Hz), 7.57 (2H, m)

Ｎ−［（４−ブロモフェニル）メチル］−Ｎ−メチル−１−ピロリジンカルボキサミド（２５０ｍｇ、粗）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１５２ｍｇ、０．８ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１６．５ｍｇ、０．１６ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、１５ｍｇ、０．０８ｍｍｏｌ）および炭酸カリウム（１．６ｍｍｏｌ、２２１ｍｇ）のジメチルスルホキシド（４ｍｌ）中混合物を、マイクロ波反応器中、１９０℃で３０分間撹拌した。反応混合物を新たなＮ，Ｎ−ジメチルグリシンおよびヨウ化銅（Ｉ）で処理し、マイクロ波反応器において１９０℃でさらに３０分間加熱した。反応混合物を、ジクロロメタン（５ｍｌ）および水（５ｍｌ）間で分配した。有機層を、５ｇのＩｓｏｌｕｔｅシリカｓｅｐ−ｐａｋカラム、酢酸エチルで溶出した。溶媒を減圧下で除去し、残渣マス・ディレクテッド自動精製（ＭＤＡＰ）により精製して、標題化合物を褐色油として得た（１２ｍｇ、４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値４０７（ＥＳ＋）、保持時間３．５０分；Ｃ_２１Ｈ_２５Ｆ_３Ｎ_４Ｏとして計算値４０６
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８５（８Ｈ，ｍ），２．６９（４Ｈ，ｍ），２．７８（３Ｈ，ｓ），３．３９（４Ｈ，ｍ），４．４６（２Ｈ，ｓ），７．３９（２Ｈ，ｄ，Ｊ＝９Ｈｚ），７．４５（２Ｈ，ｍ） Example 51: N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -1-pyrrolidinecarboxamide

N-[(4-Bromophenyl) methyl] -N-methyl-1-pyrrolidinecarboxamide (250 mg, crude), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), N, N-dimethylglycine (20 mol%, 16.5 mg, 0.16 mmol), copper (I) iodide (10 mol%, 15 mg, 0.08 mmol) and potassium carbonate (1.6 mmol, 221 mg) Of dimethyl sulfoxide (4 ml) was stirred in a microwave reactor at 190 ° C. for 30 minutes. The reaction mixture was treated with fresh N, N-dimethylglycine and copper (I) iodide and heated at 190 ° C. for an additional 30 minutes in a microwave reactor. The reaction mixture was partitioned between dichloromethane (5 ml) and water (5 ml). The organic layer was eluted with a 5 g Isolute silica sep-pak column, ethyl acetate. The solvent was removed under reduced pressure and purified by residual mass directed autopurification (MDAP) to give the title compound as a brown oil (12 mg, 4%).
LC / mass spectrum (ES): found 407 (ES +), retention time 3.50 min; calculated 406 as C ₂₁ H ₂₅ F ₃ N ₄ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.85 (8H, m), 2.69 (4H, m), 2.78 (3H, s), 3.39 (4H, m), 4.46 (2H, s), 7.39 (2H, d, J = 9 Hz), 7.45 (2H, m)

５−（４−ブロモフェニル）−２−ピロリジノン（８１ｍｇ、０．３４ｍｍｏｌ；ＷＯ００／２１９５８に記載のように調製した）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（６４ｍｇ、０．３４ｍｍｏｌ）Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、７ｍｇ、０．０７ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、６．５ｍｇ、０．０３４ｍｍｏｌ）および炭酸カリウム（０．７ｍｍｏｌ、９７ｍｇ）のジメチルスルホキシド（２ｍｌ）中混合物を、マイクロ波反応器中１９０℃で３０分間撹拌した。反応混合物を冷却し、ジクロロメタン（５ｍｌ）および水（５ｍｌ）間で分配した。有機層を、５ｇのＩｓｏｌｕｔｅシリカｓｅｐ−ｐａｋカラムに加え、酢酸エチルで溶出した。溶媒を減圧下で除去して暗い色の油を得（１６１ｍｇ）、これをさらにマス・ディレクテッド自動精製（ＭＤＡＰ）により精製して、標題化合物を黄色油として得た（１７ｍｇ、１４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３５０（ＥＳ＋）、保持時間２．９９分；Ｃ_１８Ｈ_１８Ｆ_３Ｎ_３Ｏとして計算値３４９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），１．９７（１Ｈ，ｍ），２．４８（２Ｈ，ｍ），２．５２（１Ｈ，ｍ），２．７０（４Ｈ，ｍ），４．８３（１Ｈ，ｔ，Ｊ＝７Ｈｚ），６．１３（１Ｈ，ｂｓ），７．４０（２Ｈ，ｍ），７．５１（２Ｈ，ｍ） Example 52: 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone

5- (4-Bromophenyl) -2-pyrrolidinone (81 mg, 0.34 mmol; prepared as described in WO 00/21958), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazole (64 mg, 0.34 mmol) N, N-dimethylglycine (20 mol%, 7 mg, 0.07 mmol), copper (I) iodide (10 mol%, 6.5 mg, 0.034 mmol) and potassium carbonate (0. A mixture of 7 mmol, 97 mg) in dimethyl sulfoxide (2 ml) was stirred in a microwave reactor at 190 ° C. for 30 minutes. The reaction mixture was cooled and partitioned between dichloromethane (5 ml) and water (5 ml). The organic layer was added to a 5 g Isolute silica sep-pak column and eluted with ethyl acetate. The solvent was removed under reduced pressure to give a dark oil (161 mg), which was further purified by mass directed autopurification (MDAP) to give the title compound as a yellow oil (17 mg, 14%).
LC / mass spectrum (ES): found 350 (ES +), retention time 2.99 minutes; calculated 349 as C ₁₈ H ₁₈ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 1.97 (1H, m), 2.48 (2H, m), 2.52 (1H, m), 2.70 (4H, m), 4.83 (1H, t, J = 7 Hz), 6.13 (1H, bs), 7.40 (2H, m), 7.51 (2H, m)

Ｎ−［１−（４−ブロモフェニル）エチル］アセトアミド（実施例５３）またはＮ−［１−（４−ブロモフェニル）エチル］−Ｎ−メチルアセトアミド（実施例５４）および３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例５１の方法と類似の方法を用いて、標題化合物を調製した。

Examples 53-54:

N- [1- (4-bromophenyl) ethyl] acetamide (Example 53) or N- [1- (4-bromophenyl) ethyl] -N-methylacetamide (Example 54) and 3- (trifluoromethyl) The title compound was prepared from -4,5,6,7-tetrahydro-1H-indazole using a method similar to that of Example 51.

１−アセチル−２−（４−ブロモフェニル）ピロリジン（実施例５５）、１−［２−（４−ブロモフェニル）エチル］−２−ピロリジノン（実施例５６）および３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例５２に記載の方法と類似の方法を用いて、標題化合物を調製した。

Examples 55-56:

1-acetyl-2- (4-bromophenyl) pyrrolidine (Example 55), 1- [2- (4-bromophenyl) ethyl] -2-pyrrolidinone (Example 56) and 3- (trifluoromethyl)- The title compound was prepared from 4,5,6,7-tetrahydro-1H-indazole using a method analogous to that described in Example 52.

２−［（４−ブロモフェニル）メチル］イソチアゾリジン１，１−ジオキシド（２９０ｍｇ、１．０ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１９０ｍｇ、１．０ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、２１ｍｇ、０．２ｍｍｏｌ）、ヨウ化銅（Ｉ）（１０ｍｏｌ％、１９ｍｇ、０．１ｍｍｏｌ）および炭酸カリウム（２ｍｍｏｌ、２７６ｍｇ）のジメチルスルホキシド（４ｍｌ）中混合物を、マイクロ波反応器中１９０℃で３０分間撹拌した。反応混合物をジクロロメタン（５ｍｌ）および水（５ｍｌ）間で分配した。有機層を、５ｇのＩｓｏｌｕｔｅシリカｓｅｐ−ｐａｋカラムに加え、酢酸エチルで溶出した。溶媒を減圧下で除去し、残渣を、マス・ディレクテッド自動精製（ＭＤＡＰ）により精製して灰色生成物を得、これを水およびジクロロメタン間で分配した。有機層を硫酸ナトリウムで乾燥し、空気中で蒸発させて、標題化合物を黄色油として得た（１０３ｍｇ、２６％）。
ＬＣ／マススペクトル（ＥＳ）：実測値４００（ＥＳ＋）、保持時間３．３１分；Ｃ_１８Ｈ_２０Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値３９９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．３４（２Ｈ，ｍ），２．６９（４Ｈ，ｍ），３．１２（２Ｈ，ｔ，Ｊ＝６Ｈｚ），３．２３（２Ｈ，ｔ，Ｊ＝８Ｈｚ），４．２３（２Ｈ，ｓ），７．４７（４Ｈ，ｍ） Example 57: 1- {4-[(1,1-dioxide-2-isothiazolidinyl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

2-[(4-Bromophenyl) methyl] isothiazolidine 1,1-dioxide (290 mg, 1.0 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (190 mg, 1.0 mmol), N, N-dimethylglycine (20 mol%, 21 mg, 0.2 mmol), copper (I) iodide (10 mol%, 19 mg, 0.1 mmol) and potassium carbonate (2 mmol, 276 mg) in dimethyl sulfoxide ( 4 ml) was stirred in a microwave reactor at 190 ° C. for 30 minutes. The reaction mixture was partitioned between dichloromethane (5 ml) and water (5 ml). The organic layer was added to a 5 g Isolute silica sep-pak column and eluted with ethyl acetate. The solvent was removed under reduced pressure and the residue was purified by mass directed automatic purification (MDAP) to give a gray product, which was partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate and evaporated in air to give the title compound as a yellow oil (103 mg, 26%).
LC / mass spectrum (ES): found 400 (ES +), retention time 3.31 minutes; calculated 399 as C ₁₈ H ₂₀ F ₃ N ₃ O ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.34 (2H, m), 2.69 (4H, m), 3.12 (2H, t, J = 6 Hz) , 3.23 (2H, t, J = 8 Hz), 4.23 (2H, s), 7.47 (4H, m)

典型的プロシージャ：５％ジメチルホルムアミド中の（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）アミン（記載例２０、０．２ｍｍｏｌ）のジクロロメタン（２ｍｌ）中の溶液を、トリエチルアミン（２当量、０．０５ｍｌ）で、１５ｍｌのＳａｒｓｔｅｄｔチューブ中で処理した。反応混合物を２０分間振盪し、ついで、適当な酸クロライド（０．０５ｍｌ）を加え、反応混合物を、一晩振盪した。反応混合物を、水でクエンチし、ジクロロメタンおよびブライン間で分離した。有機層を保持し、試料を、５０％石油エーテル中酢酸エチルで溶出する５ｇのプレパックシリカカラムにより（実施例５８および５９）、または、マス・ディレクテッド自動精製により（ＭＤＡＰ、実施例６０）精製した。関連フラクションを合し、溶媒をロータリーエバポレーションにより除去して、生成物を得た。

Examples 58-60:

Typical Procedure: ({4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine (Description Example 20) in 5% dimethylformamide , 0.2 mmol) in dichloromethane (2 ml) was treated with triethylamine (2 eq, 0.05 ml) in a 15 ml Sarstedt tube. The reaction mixture was shaken for 20 minutes, then the appropriate acid chloride (0.05 ml) was added and the reaction mixture was shaken overnight. The reaction mixture was quenched with water and separated between dichloromethane and brine. Retain the organic layer and purify the sample by a 5 g pre-packed silica column eluting with 50% ethyl acetate in petroleum ether (Examples 58 and 59) or by mass directed automatic purification (MDAP, Example 60). did. The relevant fractions were combined and the solvent was removed by rotary evaporation to give the product.

典型的なプロシージャ：１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（記載例１７）およびプロパンアミド（実施例６１）、アセトアミド（実施例６２）および２−フェニルアセトアミド（実施例６３）から、記載例１５に記載の方法と類似の方法を用いて標題化合物を調製した。

Examples 61-63:

Typical procedure: 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (description 17) and propanamide (Example 61) ), Acetamide (Example 62) and 2-phenylacetamide (Example 63), and the title compound was prepared using a method analogous to that described in Description Example 15.

典型的なプロシージャ：４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（１５５ｍｇ、０．５ｍｍｏｌ）、および１，１’−カルボニルジイミダゾール（１２２ｍｇ、０．７５ｍｍｏｌ）の混合物を、ジクロロメタン（２ｍｌ）中に、１５ｍｌのプラスチックチューブ中で溶解し、２０分間振盪し、ついで、二級アミンのジクロロメタン（１ｍｌ）中溶液を加えた（ＨＣｌ塩としてアミンが入手できる場合、トリエチルアミン（５１ｍｇ、０．５ｍｍｏｌ）を加えた）。反応混合物を、３時間振盪した。反応混合物をブラインで洗浄し、有機層を保持し、硫酸ナトリウムで乾燥した。すべての試料をＭＤＡＰにより精製して、生成物を調製した。

Examples 64-71:

Typical procedure: 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid (155 mg, 0.5 mmol), and 1,1′- A mixture of carbonyldiimidazole (122 mg, 0.75 mmol) was dissolved in dichloromethane (2 ml) in a 15 ml plastic tube and shaken for 20 minutes, then a solution of secondary amine in dichloromethane (1 ml) was added. (When amine was available as HCl salt, triethylamine (51 mg, 0.5 mmol) was added). The reaction mixture was shaken for 3 hours. The reaction mixture was washed with brine and the organic layer was retained and dried over sodium sulfate. All samples were purified by MDAP to prepare the product.

３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１５２ｍｇ、０．８ｍｍｏｌ）、炭酸カリウム（２３２ｍｇ、１．６８ｍｍｏｌ）およびヨウ化銅（Ｉ）（１ｍｇ、０．００５ｍｍｏｌ）の混合物を、ｔｒａｎｓ−１，２−ジアミノシクロヘキサン（９ｍｇ、０．０８ｍｍｏｌ）のジオキサン中溶液、ついで、１−（４−ブロモフェニル）イミダゾール（１６１ｍｇ、０．７２ｍｍｏｌ）のジオキサン（総容量４ｍｌ）で処理した。この混合物をマイクロ波容器中で１時間１８０℃で加熱した。さらにヨウ化銅（Ｉ）（１ｍｇ）およびｔｒａｎｓ−１，２−ジアミノシクロヘキサン（９ｍｇ）を加え、反応物をさらに１時間マイクロ波容器中１８０℃で加熱した。さらに、ヨウ化銅（Ｉ）（１ｍｇ）およびｔｒａｎｓ−１，２−ジアミノシクロヘキサン（９ｍｇ）を加え、反応物を、マイクロ波容器中１８０℃でさらに１時間加熱した。反応混合物を、５ｇのｓｅｐ−ｐａｃｋカラムに加え、酢酸エチルで溶出した。溶媒をロータリーエバポレーションにより除去し、粗生成物をさらにＭＤＡＰにより精製した。さらに１Ｍアンモニアのメタノール中溶液を用いる５ｇのＳＣＸカラムを用いて精製して、これをロータリーエバポレーションにより蒸発させて、標題化合物（４２ｍｇ、１８％）を得た。
ＬＣ／マススペクトル（ＥＳ）：実測値３３３（ＥＳ＋）、保持時間２．２１分；Ｃ_１７Ｈ_１５Ｆ_３Ｎ_４として計算値３３２
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８５（４Ｈ，ｍ），２．７３（４Ｈ，ｍ），７．２５（１Ｈ，ｍ），７．３２（１Ｈ，ｍ），７．５１（２Ｈ，ｍ），７．６３（２Ｈ，ｍ），７．８９（１Ｈ，ｓ） Example 72: 1- [4- (1H-imidazol-1-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), potassium carbonate (232 mg, 1.68 mmol) and copper (I) iodide (1 mg, .0. 005 mmol) in a solution of trans-1,2-diaminocyclohexane (9 mg, 0.08 mmol) in dioxane, followed by 1- (4-bromophenyl) imidazole (161 mg, 0.72 mmol) in dioxane (total volume 4 ml). ). The mixture was heated at 180 ° C. for 1 hour in a microwave vessel. Additional copper (I) iodide (1 mg) and trans-1,2-diaminocyclohexane (9 mg) were added and the reaction was heated at 180 ° C. in a microwave vessel for an additional hour. Further copper (I) iodide (1 mg) and trans-1,2-diaminocyclohexane (9 mg) were added and the reaction was heated in a microwave vessel at 180 ° C. for an additional hour. The reaction mixture was added to a 5 g sep-pack column and eluted with ethyl acetate. The solvent was removed by rotary evaporation and the crude product was further purified by MDAP. Further purification using a 5 g SCX column with 1 M ammonia in methanol, which was evaporated by rotary evaporation to give the title compound (42 mg, 18%).
LC / mass spectrum (ES): found 333 (ES +), retention time 2.21 min; calculated 332 as C ₁₇ H ₁₅ F ₃ N ₄
¹ H-NMR (400 MHz, CDCl ₃ ): 1.85 (4H, m), 2.73 (4H, m), 7.25 (1H, m), 7.32 (1H, m), 7.51 (2H, m), 7.63 (2H, m), 7.89 (1H, s)

（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）アミン（４３６ｍｇ、１．４８ｍｍｏｌ）のジクロロメタン中１０％ジメチルホルムアミド（５ｍｌ）中溶液を、トリエチルアミン（２．９６ｍｍｏｌ、０．４１ｍｌ）で処理した。反応混合物を５分間撹拌し、ついで、塩化２−プロペノイル（０．１３ｍｌ）を加え、反応混合物をさらに１．５時間撹拌した。反応混合物を水でクエンチし、ジクロロメタンおよびブライン間で分離した。有機層を保持し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去し、試料を、０−１００％酢酸エチル／ｎ−ペンタン溶媒勾配を用いるＢｉｏｔａｇｅ ２５＋Ｍカラムにより精製した。合した関連フラクションおよび溶媒をロータリーエバポレーションにより除去して生成物を得た。

Examples 73-74:

({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine (436 mg, 1.48 mmol) in 10% dimethylformamide in dichloromethane The solution in (5 ml) was treated with triethylamine (2.96 mmol, 0.41 ml). The reaction mixture was stirred for 5 minutes, then 2-propenoyl chloride (0.13 ml) was added and the reaction mixture was stirred for an additional 1.5 hours. The reaction mixture was quenched with water and separated between dichloromethane and brine. The organic layer was retained and dried over sodium sulfate. The solvent was removed by rotary evaporation and the sample was purified on a Biotage 25 + M column using a 0-100% ethyl acetate / n-pentane solvent gradient. The combined relevant fractions and solvent were removed by rotary evaporation to give the product.

Ｎ−（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）−２−プロペンアミド（２４１ｍｇ、０．６９ｍｍｏｌ）のジメチルホルムアミド（５ｍｌ）中撹拌溶液を、アルゴン雰囲気下、水素化ナトリウム（鉱油中６０％懸濁液、２８ｍｇ、０．７ｍｍｏｌ）で処理した。反応混合物を５分間撹拌し、ついで、ヨウ化メチル（０．０５ｍｌ）を加え、反応混合物をさらに１時間撹拌した。反応混合物を３滴の水および５ｍｌのメタノール中１Ｍアンモニア溶液でクエンチした。過剰のアンモニアおよびメタノールをロータリーエバポレーションにより除去した。反応混合物を、酢酸エチルおよびブライン間で分離した。有機層を保持し、硫酸ナトリウムで乾燥し、溶媒をロータリーエバポレーションにより除去した。試料を、５０％酢酸エチル／石油エーテルで溶出する５ｇのプレパックシリカカラムにより精製した。関連フラクションを合し、溶媒をロータリーエバポレーションにより除去して、標題化合物を黄色油として得た（６６ｍｇ、２６％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３６４（ＥＳ＋）、保持時間３．２６分；Ｃ_１９Ｈ_２０Ｆ_３Ｎ_３Ｏとして計算値３６３
^１Ｈ−ＮＭＲ（２５０ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｂｓ），２．６８（４Ｈ，ｂｓ），３．０２（３Ｈ，ｍ），４．６８（２Ｈ，ｍ），５．６８−５．８０（１Ｈ，ｍ），６．３６−４．４６（１Ｈ，ｍ），６．５２−６．７１（１Ｈ，ｍ），７．２７−７．５１（４Ｈ，ｍ） Example 75: N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide

Of N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide (241 mg, 0.69 mmol) A stirred solution in dimethylformamide (5 ml) was treated with sodium hydride (60% suspension in mineral oil, 28 mg, 0.7 mmol) under an argon atmosphere. The reaction mixture was stirred for 5 minutes, then methyl iodide (0.05 ml) was added and the reaction mixture was stirred for an additional hour. The reaction mixture was quenched with 3 drops of water and 5 ml of 1M ammonia solution in methanol. Excess ammonia and methanol were removed by rotary evaporation. The reaction mixture was separated between ethyl acetate and brine. The organic layer was retained and dried over sodium sulfate, and the solvent was removed by rotary evaporation. The sample was purified by a 5 g pre-packed silica column eluting with 50% ethyl acetate / petroleum ether. The relevant fractions were combined and the solvent was removed by rotary evaporation to give the title compound as a yellow oil (66 mg, 26%).
LC / mass spectrum (ES): found 364 (ES +), retention time 3.26 min; calculated as C ₁₉ H ₂₀ F ₃ N ₃ O 363
¹ H-NMR (250 MHz, CDCl ₃ ): 1.82 (4H, bs), 2.68 (4H, bs), 3.02 (3H, m), 4.68 (2H, m), 5.68 -5.80 (1H, m), 6.36-4.46 (1H, m), 6.52-6.71 (1H, m), 7.27-7.51 (4H, m)

典型的なプロシージャ：｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸（９０ｍｇ、０．２８ｍｍｏｌ）、および１−ヒドロキシベンゾトリアゾール（４５ｍｇ、０．３３ｍｍｏｌ）の混合物を、乾燥アセトニトリル中でスラリーとして撹拌した。１−（３−ジメチルアミノプロピル）−３−エチルカルボジイミド塩酸塩（ＥＤＣ）（６１ｍｇ、０．３２ｍｍｏｌ）を一度に加え、反応混合物を３０分室温にて撹拌した。適当なアミドキシムを一度に加え、反応物を、４Åモレキュラーシーブの存在下、４時間加熱還流した。さらに、０．５当量の１−（３−ジメチルアミノプロピル）−３−エチルカルボジイミド塩酸得を加え、還流を４〜６時間続けた。反応混合物を蒸発させて残渣を乾燥し、酢酸エチルおよび飽和炭酸水素ナトリウム水溶液間で分離した。有機層を保持し、溶媒をロータリーエバポレーションにより除去し、試料をＭＤＡＰにより精製した。関連フラクションを合し、溶媒をロータリーエバポレーションにより除去して生成物を得た。

Examples 76-77:

Typical procedure: {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid (90 mg, 0.28 mmol), and 1-hydroxy A mixture of benzotriazole (45 mg, 0.33 mmol) was stirred as a slurry in dry acetonitrile. 1- (3-Dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) (61 mg, 0.32 mmol) was added in one portion and the reaction mixture was stirred for 30 minutes at room temperature. Appropriate amidoxime was added in one portion and the reaction was heated to reflux for 4 hours in the presence of 4Å molecular sieves. Further, 0.5 equivalent of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride was added and refluxing was continued for 4-6 hours. The reaction mixture was evaporated and the residue was dried and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was retained, the solvent was removed by rotary evaporation and the sample was purified by MDAP. The relevant fractions were combined and the solvent was removed by rotary evaporation to give the product.

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（３１０ｍｇ、１．０ｍｍｏｌ）のジクロロメタン（５ｍｌ）中懸濁液を、１，１’−カルボニルジイミダゾール（１６２ｍｇ、１．０ｍｍｏｌ）でアルゴン雰囲気下室温にて処理した。この混合物を３０分間撹拌し、ついで、２Ｍのエチルアミン中テトラヒドロフラン（０．５ｍｌ）溶液で処理した。混合物すべてを室温にて２時間撹拌した。反応混合物を飽和炭酸水素ナトリウム水溶液で洗浄した。有機層を分離し、硫酸ナトリウムで乾燥し、ロータリーエバポレーションにより最小容量にして、ベージュの固体を得（２５０ｍｇ）、これを、０−５０％石油エーテル中酢酸エチルで溶出する５ｇのプレパックシリカカラムのカラムクロマトグラフィーにより精製して、標題化合物を無色の固体として得た（１２８ｍｇ、３８％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３３８（ＥＳ＋）、保持時間３．１３分；Ｃ_１７Ｈ_１８Ｆ_３Ｎ_３Ｏとして計算値３３７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．２８（３Ｈ，ｔ，Ｊ＝７Ｈｚ），１．８３（４Ｈ，ｍ），２．６８（２Ｈ，ｂｓ），２．７４（２Ｈ，ｂｓ），３．５３（２Ｈ，ｍ），６．１５（１Ｈ，ｂｓ），７．５９（２Ｈ，ｍ），７．８９（２Ｈ，ｍ） Example 78: N-ethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

A suspension of 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid (310 mg, 1.0 mmol) in dichloromethane (5 ml) was added 1 , 1′-carbonyldiimidazole (162 mg, 1.0 mmol) was treated at room temperature under an argon atmosphere. The mixture was stirred for 30 minutes and then treated with 2M solution in tetrahydrofuran (0.5 ml) in ethylamine. All the mixtures were stirred at room temperature for 2 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate. The organic layer was separated, dried over sodium sulfate and minimized by rotary evaporation to give a beige solid (250 mg) which was eluted with 0-50% ethyl acetate in petroleum ether, a 5 g pre-packed silica column. Of the title compound as a colorless solid (128 mg, 38%).
LC / Mass Spec (ES): Found 338 (ES +), retention time 3.13 _{min; C 17 H 18 F 3 N} 3 O Calculated 337
¹ H-NMR (400 MHz, CDCl ₃ ): 1.28 (3H, t, J = 7 Hz), 1.83 (4H, m), 2.68 (2H, bs), 2.74 (2H, bs) , 3.53 (2H, m), 6.15 (1H, bs), 7.59 (2H, m), 7.89 (2H, m)

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（ＭＷｔ＝３１０）のジクロロメタン（２ｍｌ）中溶液を、１，１’−カルボニルジイミダゾール（１当量、ＭＷｔ＝１６２）で処理し、室温にて１５分間撹拌した。ついで、二級アミン（１．１５当量）を加え、１時間撹拌し続けた。反応混合物を、４０−６０℃石油エーテル中０〜５０％酢酸エチルで溶出する５ｇのプレパックシリカカラムで精製した。生成物をさらにＭＤＡＰにより精製して、記載の化合物を得た。

Examples 79-81:

A solution of 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid (MWt = 310) in dichloromethane (2 ml) was added to 1,1′- Treated with carbonyldiimidazole (1 equivalent, MWt = 162) and stirred at room temperature for 15 minutes. Then secondary amine (1.15 eq) was added and stirring continued for 1 hour. The reaction mixture was purified on a 5 g pre-packed silica column eluting with 0-50% ethyl acetate in 40-60 ° C. petroleum ether. The product was further purified by MDAP to give the described compound.

４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］安息香酸（８７ｍｇ、０．２８ｍｍｏｌ）およびジイソプロピルエチルアミン（０．１ｍｌ）のジクロロメタン（３ｍｌ）中溶液を、１，１’−カルボニルジイミダゾール（４６ｍｇ、０．２８ｍｍｏｌ）で処理し、室温にて１５分間撹拌した。ついで、メチルアミン塩酸塩（２２ｍｇ、０．３３ｍｍｏｌ）を加え、１時間撹拌し続けた。反応混合物を、５ｇのプレパックシリカカラムに加え、０−５０％石油エーテル中酢酸エチルで溶出して、標題化合物（２８ｍｇ、３１％）を得た。
ＬＣ／マススペクトル（ＥＳ）：実測値３２４（ＥＳ＋）、保持時間３．０４分；Ｃ_１６Ｈ_１６Ｆ_３Ｎ_３Ｏとして計算値３２３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．６８（２Ｈ，ｂｓ），２．７５（２Ｈ，ｂｓ），３．０５（３Ｈ，ｄ，Ｊ＝５Ｈｚ），６．１７（１Ｈ，ｍ），７．５９（２Ｈ，ｍ），７．８７（２Ｈ，ｍ） Example 82: N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide

4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzoic acid (87 mg, 0.28 mmol) and diisopropylethylamine (0.1 ml) in dichloromethane (3 ml The solution in) was treated with 1,1′-carbonyldiimidazole (46 mg, 0.28 mmol) and stirred at room temperature for 15 minutes. Methylamine hydrochloride (22 mg, 0.33 mmol) was then added and stirring continued for 1 hour. The reaction mixture was added to a 5 g pre-packed silica column and eluted with 0-50% ethyl acetate in petroleum ether to give the title compound (28 mg, 31%).
LC / mass spectrum (ES): found 324 (ES +), retention time 3.04 minutes; calculated 323 as C ₁₆ H ₁₆ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.68 (2H, bs), 2.75 (2H, bs), 3.05 (3H, d, J = 5 Hz) 6.17 (1H, m), 7.59 (2H, m), 7.87 (2H, m)

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝酢酸（６５ｍｇ、０．２ｍｍｏｌ）のジクロロメタン（２ｍｌ）中溶液を、１，１’−カルボニルジイミダゾール（３２．５ｍｇ、０．２ｍｍｏｌ）で室温にて処理し、室温にて１５分間撹拌した。ついで、２−フェニルピロリジン（２９ｍｇ、０．２ｍｍｏｌ）を加え、１時間撹拌し続けた。溶媒の大部分を減圧下で除去し、粗生成物さらに、ＭＤＡＰにより精製して、標題化合物（５５ｍｇ、６１％）を得た。
ＬＣ／マススペクトル（ＥＳ）：実測値４５４（ＥＳ＋）、保持時間３．６１分；Ｃ_２６Ｈ_２６Ｆ_３Ｎ_３Ｏとして計算値４５３ Example 83: 1- {4- [2-oxo-2- (2-phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazole

A solution of {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetic acid (65 mg, 0.2 mmol) in dichloromethane (2 ml) was added 1 , 1'-carbonyldiimidazole (32.5 mg, 0.2 mmol) at room temperature and stirred at room temperature for 15 minutes. Then 2-phenylpyrrolidine (29 mg, 0.2 mmol) was added and stirring continued for 1 hour. Most of the solvent was removed under reduced pressure and the crude product was further purified by MDAP to give the title compound (55 mg, 61%).
LC / mass spectrum (ES): found 454 (ES +), retention time 3.61 minutes; calculated as C ₂₆ H ₂₆ F ₃ N ₃ O 453

｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メタノール（２８６ｍｇ、０．９７ｍｍｏｌ）をジクロロメタン（５ｍｌ）中に溶解し、アルゴン雰囲気下、メタノール／氷浴中で撹拌した。トリエチルアミン（１０６ｍｇ、１．０５ｍｍｏｌ、０．１５ｍｌ）を一度に加え、反応混合物をさらに１５分間撹拌した。メタンスルホニルクロライド（１１５ｍｇ、１ｍｍｏｌ、０．０８ｍｌ）を１０分にわたって滴下した。反応混合物をさらに１０分間０℃以下で撹拌し、室温に戻した。反応混合物を、ジクロロメタン（５ｍｌ）および水（３０ｍｌ）間で分離した。有機層を保持し、硫酸ナトリウムを用いて乾燥し、溶媒をロータリーエバポレーションにより除去して、粗メシレート（Ａ）（２９９ｍｇ）を得た。
Ｎ−メチルベンズアミド（２０ｍｇ、０．１４ｍｍｏｌ）を、ジメチルホルムアミド（１ｍｌ）中に溶解し、１５ｍｌのプラスチックチューブ中で振盪した。水素化ナトリウム（鉱油中６０％懸濁液、６ｍｇ、０．１５ｍｍｏｌ）を一度に加え、反応物を１５分間振盪した。メシレート（Ａ）（５０ｍｇ、０．１３ｍｍｏｌ）のジメチルホルムアミド（１ｍｌ）中溶液を、１０分にわたって滴下した。反応混合物をさらに３０分間振盪した。ついで、反応容器をアルゴンでフラッシュし、３日間振盪した。反応混合物を、ジクロロメタン（３０ｍｌ）および水（２０ｍｌ）で分離し、ブライン（１０ｍｌ）で洗浄した。ジクロロメタン層を、水（２×２０ｍｌ）で洗浄し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去し、試料をＭＤＡＰにより精製した。関連フラクションを合し、溶媒をロータリーエバポレーションにより除去して、標題化合物を得た（４ｍｇ、７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値４１４（ＥＳ＋）、保持時間３．５７分；Ｃ_２３Ｈ_２２Ｆ_３Ｎ_３Ｏとして計算値４１３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），２．８９および３．０６（３Ｈ，ｍ，回転異性体），４．５７および４．８１（２Ｈ，ｍ，回転異性体），７．３５−７．５２（９Ｈ，ｍ） Example 84: N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide

{4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanol (286 mg, 0.97 mmol) was dissolved in dichloromethane (5 ml), Stir in a methanol / ice bath under an argon atmosphere. Triethylamine (106 mg, 1.05 mmol, 0.15 ml) was added in one portion and the reaction mixture was stirred for an additional 15 minutes. Methanesulfonyl chloride (115 mg, 1 mmol, 0.08 ml) was added dropwise over 10 minutes. The reaction mixture was stirred for an additional 10 minutes below 0 ° C. and allowed to warm to room temperature. The reaction mixture was separated between dichloromethane (5 ml) and water (30 ml). The organic layer was retained and dried using sodium sulfate, and the solvent was removed by rotary evaporation to give crude mesylate (A) (299 mg).
N-methylbenzamide (20 mg, 0.14 mmol) was dissolved in dimethylformamide (1 ml) and shaken in a 15 ml plastic tube. Sodium hydride (60% suspension in mineral oil, 6 mg, 0.15 mmol) was added in one portion and the reaction was shaken for 15 minutes. A solution of mesylate (A) (50 mg, 0.13 mmol) in dimethylformamide (1 ml) was added dropwise over 10 minutes. The reaction mixture was shaken for an additional 30 minutes. The reaction vessel was then flushed with argon and shaken for 3 days. The reaction mixture was separated with dichloromethane (30 ml) and water (20 ml) and washed with brine (10 ml). The dichloromethane layer was washed with water (2 × 20 ml) and dried over sodium sulfate. The solvent was removed by rotary evaporation and the sample was purified by MDAP. The relevant fractions were combined and the solvent was removed by rotary evaporation to give the title compound (4 mg, 7%).
LC / mass spectrum (ES): found 414 (ES +), retention time 3.57 minutes; calculated 413 as C ₂₃ H ₂₂ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.70 (4H, m), 2.89 and 3.06 (3H, m, rotamer), 4.57 and 4.81 (2H, m, rotamer), 7.35-7.52 (9H, m)

３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１５２ｍｇ、０．８ｍｍｏｌ）、５−（４−ブロモフェニル）−１，３−オキサゾール（１７９ｍｇ、０．８ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（１６ｍｇ、０．１６ｍｍｏｌ）、ヨウ化銅（Ｉ）（１６ｍｇ、０．０８ｍｍｏｌ）、炭酸カリウム（２３５ｍｇ、１．７ｍｍｏｌ）のジメチルスルホキシド（３ｍｌ）中混合物を、マイクロ波反応器中１８０℃で合計６０分間加熱した。反応混合物を、４０ｍｌの１：１石油エーテル中酢酸エチルを用いる５ｇのｓｅｐ−ｐａｃｋカラムにより精製した。溶媒をロータリーエバポレーションにより除去し、残渣を酢酸エチル（２０ｍｌ）および水（２０ｍｌ）間で分配した。有機層を保持し、ブライン（２×１０ｍｌ）で洗浄した。有機物質をＭＤＡＰにより精製した。関連フラクションを合し、溶媒をロータリーエバポレーションにより除去して、記載の生成物を得た。ついで、生成物を、ジクロロメタン（４０ｍｌ）および水（４０ｍｌ）間で分配した。有機層を保持し、溶媒をロータリーエバポレーションにより除去して、標題化合物を得た（８０ｍｇ、３０％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３３４（ＥＳ＋）、保持時間３．５７分；Ｃ_１７Ｈ_１４Ｆ_３Ｎ_３Ｏとして計算値３３３
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８３（４Ｈ，ｍ），２．６９（２Ｈ，ｂｓ），２．７４（２Ｈ，ｂｓ），７．４２（１Ｈ，ｓ），７．５８（２Ｈ，ｍ），７．７６（２Ｈ，ｍ），７．９６（１Ｈ，ｍ） Example 85: 1- [4- (1,3-oxazol-5-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), 5- (4-bromophenyl) -1,3-oxazole (179 mg, 0.8 mmol) , N, N-dimethylglycine (16 mg, 0.16 mmol), copper (I) iodide (16 mg, 0.08 mmol), potassium carbonate (235 mg, 1.7 mmol) in dimethyl sulfoxide (3 ml) was microwaved. Heated in the reactor at 180 ° C. for a total of 60 minutes. The reaction mixture was purified by a 5 g sep-pack column using 40 ml of ethyl acetate in 1: 1 petroleum ether. The solvent was removed by rotary evaporation and the residue was partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was retained and washed with brine (2 × 10 ml). The organic material was purified by MDAP. The relevant fractions were combined and the solvent was removed by rotary evaporation to give the described product. The product was then partitioned between dichloromethane (40 ml) and water (40 ml). The organic layer was retained and the solvent was removed by rotary evaporation to give the title compound (80 mg, 30%).
LC / mass spectrum (ES): found 334 (ES +), retention time 3.57 min; calculated 333 as C ₁₇ H ₁₄ F ₃ N ₃ O
¹ H-NMR (400 MHz, CDCl ₃ ): 1.83 (4H, m), 2.69 (2H, bs), 2.74 (2H, bs), 7.42 (1H, s), 7.58 (2H, m), 7.76 (2H, m), 7.96 (1H, m)

３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１５２ｍｇ、０．８ｍｍｏｌ）、１−ブロモ−４−（プロピルオキシ）ベンゼン（１７７ｍｇ、０．８ｍｍｏｌ）、Ｎ，Ｎ−ジメチルグリシン（１６ｍｇ、０．１６ｍｍｏｌ）、ヨウ化銅（Ｉ）（１６ｍｇ、０．０８ｍｍｏｌ）、炭酸カリウム（２３５ｍｇ、１．７ｍｍｏｌ）のジメチルスルホキシド（３ｍｌ）中混合物を、マイクロ波反応器中、合計５０分間１８０℃で加熱した。フラッシュＮ，Ｎ−ジメチルグリシン（１６ｍｇ、０．１６ｍｍｏｌ）およびヨウ化銅（Ｉ）（１６ｍｇ、０．０８ｍｍｏｌ）を加え、１８０℃でさらに３０分間加熱した。反応混合物を、４０ｍｌの１：１石油エーテル中酢酸エチルを用いる５ｇ ｓｅｐ−ｐａｃｋカラムにより濾過した。溶媒をロータリーエバポレーションにより除去し、残渣を酢酸エチル（２０ｍｌ）および水（２０ｍｌ）間で分配した。有機層を保持し、ブライン（２×１０ｍｌ）で洗浄し、ついで、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去し、試料をＭＤＡＰにより精製した。関連フラクションを合し、溶媒をロータリーエバポレーションにより除去して、標題化合物を得た（２３ｍｇ、９％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３２５（ＥＳ＋）、保持時間４．０１分；Ｃ_１７Ｈ_１９Ｆ_３Ｎ_２Ｏとして計算値３２４
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．０５（３Ｈ，ｔ，Ｊ＝８Ｈｚ），１．８３（６Ｈ，ｍ），２．６５（４Ｈ，ｍ），３．９５（２Ｈ，ｔ，Ｊ＝７Ｈｚ），６．９６（２Ｈ，ｍ），７．３６（２Ｈ，ｍ） Example 86: 1- [4- (propyloxy) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), 1-bromo-4- (propyloxy) benzene (177 mg, 0.8 mmol), N, A mixture of N-dimethylglycine (16 mg, 0.16 mmol), copper (I) iodide (16 mg, 0.08 mmol), potassium carbonate (235 mg, 1.7 mmol) in dimethyl sulfoxide (3 ml) was placed in a microwave reactor. And heated at 180 ° C. for a total of 50 minutes. Flash N, N-dimethylglycine (16 mg, 0.16 mmol) and copper (I) iodide (16 mg, 0.08 mmol) were added and heated at 180 ° C. for an additional 30 minutes. The reaction mixture was filtered through a 5 g sep-pack column using 40 ml of ethyl acetate in 1: 1 petroleum ether. The solvent was removed by rotary evaporation and the residue was partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was retained and washed with brine (2 × 10 ml) then dried over sodium sulfate. The solvent was removed by rotary evaporation and the sample was purified by MDAP. The relevant fractions were combined and the solvent was removed by rotary evaporation to give the title compound (23 mg, 9%).
LC / Mass Spec (ES): Found 325 (ES +), retention time 4.01 _{min; C 17 H 19 F 3 N} 2 O Calculated 324
¹ H-NMR (400 MHz, CDCl ₃ ): 1.05 (3H, t, J = 8 Hz), 1.83 (6H, m), 2.65 (4H, m), 3.95 (2H, t, J = 7 Hz), 6.96 (2H, m), 7.36 (2H, m)

ヨウ化銅（Ｉ）（１０ｍｏｌ％、５ｍｇ、０．０２ｍｍｏｌ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（５０ｍｇ、０．２６ｍｍｏｌ）、炭酸カリウム（７３ｍｇ、０．５２ｍｍｏｌ）のＤＭＳＯ（２ｍｌ）中混合物を、１分間撹拌し、ついで、４−（４−ブロモフェニル）−１−メチル−１Ｈ−イミダゾール（６２ｍｇ、０．２６ｍｍｏｌ）（ＷＯ９１／０９８５５）およびＮ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、５．４ｍｇ）を連続して加えた。反応チューブをすぐにシールし、内容物をマイクロ波反応器中１８０℃で４０分間加熱した。反応混合物を酢酸エチルおよび水間で分配し、硫酸ナトリウムで乾燥し、溶媒をロータリーエバポレーションにより除去し、試料をＭＤＡＰにより精製した。溶媒をロータリーエバポレーションにより除去して、標題化合物を固体として得た（１５ｍｇ、１６％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３４７（ＥＳ＋）、保持時間２．２３分；Ｃ_１８Ｈ_１７Ｆ_３Ｎ_４として計算値３４６
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．８２（４Ｈ，ｍ），２．７０（４Ｈ，ｍ），３．７５（３Ｈ，ｓ），７．２３（１Ｈ，ｍ），７．４８（３Ｈ，ｄ，Ｊ＝８．８Ｈｚ），７．８３（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ） Example 87: 1- [4- (1-Methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

Copper (I) iodide (10 mol%, 5 mg, 0.02 mmol), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (50 mg, 0.26 mmol), potassium carbonate (73 mg , 0.52 mmol) in DMSO (2 ml) was stirred for 1 min, followed by 4- (4-bromophenyl) -1-methyl-1H-imidazole (62 mg, 0.26 mmol) (WO 91/09855) and N, N-dimethylglycine (20 mol%, 5.4 mg) was added continuously. The reaction tube was immediately sealed and the contents heated in a microwave reactor at 180 ° C. for 40 minutes. The reaction mixture was partitioned between ethyl acetate and water, dried over sodium sulfate, the solvent was removed by rotary evaporation, and the sample was purified by MDAP. The solvent was removed by rotary evaporation to give the title compound as a solid (15 mg, 16%).
LC / mass spectrum (ES): Found 347 (ES +), retention time 2.23 _{min; C 18 H 17 F 3 N} 4 Calculated 346
¹ H-NMR (400 MHz, CDCl ₃ ): 1.82 (4H, m), 2.70 (4H, m), 3.75 (3H, s), 7.23 (1H, m), 7.48 (3H, d, J = 8.8 Hz), 7.83 (2H, d, J = 8.4 Hz)

（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）アミン（１００ｍｇ、０．３３９ｍｍｏｌ）、トリエチルアミン（０．０７ｍｌ、０．５１ｍｍｏｌ）のＤＣＭ（１０ｍｌ）中混合物を、アルゴン雰囲気下氷浴中で撹拌した。ついで、ＤＣＭ（１ｍｌ）中のイソプロピルスルホニルクロライド（合計で１４８ｍｇ、１ｍｍｏｌ）を撹拌しながら滴下した。反応混合物を、１６時間室温にて撹拌し、ついで、反応混合物を水（２０ｍｌ）で洗浄し、有機層を分離し、硫酸ナトリウムで乾燥した。溶媒をロータリーエバポレーションにより除去し、試料をＭＤＡＰにより精製して、標題化合物を灰白色固体として得た（５１ｍｇ、３７％）。
ＬＣ／マススペクトル（ＥＳ）：実測値４０２（ＥＳ＋）、保持時間３．４０分；Ｃ_１８Ｈ_２２Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値４０１
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．４（６Ｈ，ｄ，Ｊ＝６．８Ｈｚ），１．８（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．１２（１Ｈ，ｍ），４．３６（３Ｈ，ｍ），７．４７（４Ｈ，ｍ） Example 88: N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propanesulfonamide

({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine (100 mg, 0.339 mmol), triethylamine (0.07 ml, 0.51 mmol) in DCM (10 ml) was stirred in an ice bath under an argon atmosphere. Then isopropylsulfonyl chloride (total 148 mg, 1 mmol) in DCM (1 ml) was added dropwise with stirring. The reaction mixture was stirred for 16 hours at room temperature, then the reaction mixture was washed with water (20 ml) and the organic layer was separated and dried over sodium sulfate. The solvent was removed by rotary evaporation and the sample was purified by MDAP to give the title compound as an off-white solid (51 mg, 37%).
LC / mass spectrum (ES): found 402 (ES +), retention time 3.40 min; calculated 401 as C ₁₈ H ₂₂ F ₃ N ₃ O ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 1.4 (6H, d, J = 6.8 Hz), 1.8 (4H, m), 2.68 (4H, m), 3.12 (1H, m), 4.36 (3H, m), 7.47 (4H, m)

（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）アミンおよびシクロプロパンスルホニルクロライドから、実施例８８に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４００（ＥＳ＋）、保持時間３．３５分；Ｃ_１８Ｈ_２０Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値３９９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：０．９（２Ｈ，ｍ），１．１７（２Ｈ，ｍ），１．８０（４Ｈ，ｍ），２．３７（１Ｈ，ｍ），２．７０（４Ｈ，ｍ），４．４０（２Ｈ，ｄ，Ｊ＝６Ｈｚ），４．６２（１Ｈ，ｍ），７．４３７．５４（４Ｈ，ｍ） Example 89: N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide

The method described in Example 88 from ({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine and cyclopropanesulfonyl chloride. The title compound was prepared using a method similar to.
LC / mass spectrum (ES): found 400 (ES +), retention time 3.35 minutes; calculated 399 as C ₁₈ H ₂₀ F ₃ N ₃ O ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 0.9 (2H, m), 1.17 (2H, m), 1.80 (4H, m), 2.37 (1H, m), 2.70 (4H, m), 4.40 (2H, d, J = 6 Hz), 4.62 (1H, m), 7.437.54 (4H, m)

（｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝メチル）アミンおよびシクロペンタンスルホニルクロライドから、実施例８８に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４２８（ＥＳ＋）、保持時間３．４１分；Ｃ_２０Ｈ_２４Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値４２７
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６２（２Ｈ，ｍ），１．８０（６Ｈ，ｍ），２．０（４Ｈ，ｍ），２．６８（４Ｈ，ｍ），３．４０（１Ｈ，ｍ），４．３８（２Ｈ，ｍ），４．４６（１Ｈ，ｍ），７．４２７．５２（４Ｈ，ｍ） Example 90: N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide

The method described in Example 88 from ({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) amine and cyclopentanesulfonyl chloride. The title compound was prepared using a method similar to.
LC / Mass Spec (ES): Found 428 (ES +), retention time 3.41 _{min; C 20 H 24 F 3 N} 3 O 2 S Calculated 427
¹ H-NMR (400 MHz, CDCl ₃ ): 1.62 (2H, m), 1.80 (6H, m), 2.0 (4H, m), 2.68 (4H, m), 3.40 (1H, m), 4.38 (2H, m), 4.46 (1H, m), 7.427.52 (4H, m)

１−［（４−ヨウドフェニル）スルホニル］ピロリジンおよび３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールから、実施例８７に記載の方法と類似の方法を用いて、標題化合物を調製した。
ＬＣ／マススペクトル（ＥＳ）：実測値４００（ＥＳ＋）、保持時間３．５９分；Ｃ_１８Ｈ_２０Ｆ_３Ｎ_３Ｏ_２Ｓとして計算値３９９
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７７（４Ｈ，ｍ），１．８４（４Ｈ，ｍ），２．６７（２Ｈ，ｍ），２．７６（２Ｈ，ｍ），３．２７（４Ｈ，ｍ），７．６９（２Ｈ，ｍ），７．９４（２Ｈ，ｍ） Example 91: 1- [4- (1-pyrrolidinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

From 1-[(4-iodophenyl) sulfonyl] pyrrolidine and 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole using a method similar to that described in Example 87. The title compound was prepared.
LC / mass spectrum (ES): found 400 (ES +), retention time 3.59 min; calculated 399 as C ₁₈ H ₂₀ F ₃ N ₃ O ₂ S
¹ H-NMR (400 MHz, CDCl ₃ ): 1.77 (4H, m), 1.84 (4H, m), 2.67 (2H, m), 2.76 (2H, m), 3.27 (4H, m), 7.69 (2H, m), 7.94 (2H, m)

典型的なプロシージャ：ヨウ化銅（Ｉ）（２０ｍｏｌ％、２０ｍｇ）、３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（１００ｍｇ、０．５３ｍｍｏｌ）、炭酸カリウム（１４６ｍｇ、１．０５ｍｍｏｌ）のＤＭＳＯ（２ｍｌ）中混合物を、１分間撹拌し、ついで、４−ヨウドベンゼンスルホンアミド誘導体（０．５３ｍｍｏｌ）およびＮ，Ｎ−ジメチルグリシン（２０ｍｏｌ％、１０ｍｇ）を連続して加えた。反応チューブをすぐにシールし、内容物をマイクロ波反応器中１８０℃で４０分間加熱した。反応混合物を酢酸エチルおよび水間で分配し、硫酸ナトリウムで乾燥し、溶媒をロータリーエバポレーションにより除去し、試料をＭＤＡＰにより精製した。溶媒をロータリーエバポレーションにより除去して、記載の生成物を得た。

Examples 92-96:

Typical procedure: copper (I) iodide (20 mol%, 20 mg), 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (100 mg, 0.53 mmol), potassium carbonate ( 146 mg, 1.05 mmol) in DMSO (2 ml) was stirred for 1 min, then 4-iodobenzenesulfonamide derivative (0.53 mmol) and N, N-dimethylglycine (20 mol%, 10 mg) in succession. Added. The reaction tube was immediately sealed and the contents heated in a microwave reactor at 180 ° C. for 40 minutes. The reaction mixture was partitioned between ethyl acetate and water, dried over sodium sulfate, the solvent was removed by rotary evaporation, and the sample was purified by MDAP. The solvent was removed by rotary evaporation to give the described product.

水素化ナトリウム（鉱油中６０％、１４．０ｍｇ；０．３５ｍｍｏｌ）を、イミダゾール（１１．５ｍｇ；０．１７ｍｍｏｌ）の無水ＤＭＦ（１ｍＬ）中撹拌溶液（室温）に加えた。この温度で１時間撹拌した後、１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（６１．２ｍｇ；０．１９ｍｍｏｌ）の無水ＤＭＦ（０．４ｍＬ）中溶液を加え、得られた混合物を室温にてさらに１６時間撹拌した。反応物を、塩酸（０．２Ｍ；０．２ｍＬ）でクエンチし、ＳＣＸカラムクロマトグラフィーにより精製して、標題化合物を黄色油として得た（５１．８ｍｇ；８９％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３４７（ＥＳ＋）、保持時間２．１８分；Ｃ_１８Ｈ_１７Ｆ_３Ｎ_４として計算値３４６
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７７−１．９５（４Ｈ，ｍ），２．６０−２．７４（４Ｈ，ｍ），５．１８（２Ｈ，ｓ），６．９０−６．９３（１Ｈ，ｍ），７．１２（１Ｈ，ａｐｐ ｓ），７．２２−７．２９（２Ｈ，ｍ），７．４７−７．５２（２Ｈ，ｍ），７．５６（１Ｈ，ａｐｐ ｓ） Example 97: 1- [4- (1H-imidazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

Sodium hydride (60% in mineral oil, 14.0 mg; 0.35 mmol) was added to a stirred solution (room temperature) of imidazole (11.5 mg; 0.17 mmol) in anhydrous DMF (1 mL). After stirring at this temperature for 1 hour, 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (61.2 mg; 0.19 mmol) ) In anhydrous DMF (0.4 mL) was added and the resulting mixture was stirred at room temperature for an additional 16 hours. The reaction was quenched with hydrochloric acid (0.2M; 0.2 mL) and purified by SCX column chromatography to give the title compound as a yellow oil (51.8 mg; 89%).
LC / mass spectrum (ES): found 347 (ES +), retention time 2.18 minutes; calculated 346 as C ₁₈ H ₁₇ F ₃ N ₄
¹ H-NMR (400 MHz, CDCl ₃ ): 1.77-1.95 (4H, m), 2.60-2.74 (4H, m), 5.18 (2H, s), 6.90- 6.93 (1H, m), 7.12 (1H, app s), 7.22-7.29 (2H, m), 7.47-7.52 (2H, m), 7.56 (1H , App s)

Example: 98-99
Similar to the method described in Example 97 from 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and the appropriate azole heterocycle. Example compounds were prepared by the method described above.

水素化ナトリウム（鉱油中６０％、１１．０ｍｇ；０．２８ｍｍｏｌ）を、１，２，３−トリアゾール（１１．３ｍｇ；０．１６ｍｍｏｌ）の無水ＤＭＦ（１ｍＬ）中撹拌溶液（室温）に加えた。この温度で１時間撹拌した後、１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（６１．２ｍｇ；０．１９ｍｍｏｌ）の無水ＤＭＦ（０．４ｍＬ）中溶液を加え
得られた混合物を室温にてさらに１６時間撹拌した。反応物を、塩酸（０．２Ｍ；０．２ｍＬ）でクエンチし、ＳＣＸカラムにより濾過した。濾液をＭＤＡＰにより精製して、実施例１０１を得た（１１．７ｍｇ；２１％）。ＳＣＸカラムクロマトグラフィーの一部として、ＳＣＸカラムをメタノール性アンモニアでフラッシュして、実施例１００（９．１ｍｇ；１６％）を得た。

Examples 100-101:

Sodium hydride (60% in mineral oil, 11.0 mg; 0.28 mmol) was added to a stirred solution (room temperature) of 1,2,3-triazole (11.3 mg; 0.16 mmol) in anhydrous DMF (1 mL). . After stirring at this temperature for 1 hour, 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (61.2 mg; 0.19 mmol) ) In anhydrous DMF (0.4 mL) was added and the resulting mixture was stirred at room temperature for an additional 16 hours. The reaction was quenched with hydrochloric acid (0.2M; 0.2 mL) and filtered through an SCX column. The filtrate was purified by MDAP to give Example 101 (11.7 mg; 21%). As part of the SCX column chromatography, the SCX column was flushed with methanolic ammonia to give Example 100 (9.1 mg; 16%).

水素化ナトリウム（鉱油中６０％、１０．０ｍｇ；０．２５ｍｍｏｌ）を、４−メチル−１Ｈ−ピラゾール（１５．０ｍｇ；０．１８ｍｍｏｌ）の無水ＤＭＦ（１ｍＬ）中撹拌溶液（室温）に加えた。この温度で１５分間撹拌した後、１−［４−（クロロメチル）フェニル］−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（５２．０ｍｇ；０．１６ｍｍｏｌ）の無水ＤＭＦ（１ｍＬ）中溶液を加え、得られた混合物を室温にてさらに２３時間撹拌した。反応物を塩酸（２Ｍ；１ｍＬ）でクエンチし、減圧下で濃縮し、ＭＤＡＰにより精製して、標題化合物を得た（３５．６ｍｇ；６０％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３６１（ＥＳ＋）、保持時間３．４２分；Ｃ_１９Ｈ_１９Ｆ_３Ｎ_４として計算値３６０
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．７６−１．８９（４Ｈ，ｍ），２．０８（３Ｈ，ｓ），２．６１−２．７４（４Ｈ，ｍ），５．２９（２Ｈ，ｓ），７．１６（１Ｈ，ｓ），７．２３−７．３１（２Ｈ，ｍ），７．３６（１Ｈ，ｓ），７．４２−７．４８（２Ｈ，ｍ） Example 102: 1- {4-[(4-Methyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole

Sodium hydride (60% in mineral oil, 10.0 mg; 0.25 mmol) was added to a stirred solution of 4-methyl-1H-pyrazole (15.0 mg; 0.18 mmol) in anhydrous DMF (1 mL) (room temperature). . After stirring at this temperature for 15 minutes, 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (52.0 mg; 0.16 mmol ) In anhydrous DMF (1 mL) was added and the resulting mixture was stirred at room temperature for an additional 23 hours. The reaction was quenched with hydrochloric acid (2M; 1 mL), concentrated under reduced pressure and purified by MDAP to give the title compound (35.6 mg; 60%).
LC / mass spectrum (ES): found 361 (ES +), retention time 3.42 minutes; calculated as C ₁₉ H ₁₉ F ₃ N ₄ 360
¹ H-NMR (400 MHz, CDCl ₃ ): 1.76-1.89 (4H, m), 2.08 (3H, s), 2.61-2.74 (4H, m), 5.29 ( 2H, s), 7.16 (1H, s), 7.23-7.31 (2H, m), 7.36 (1H, s), 7.42-7.48 (2H, m)

Examples: 103-111 Example 102 from 1- [4- (chloromethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and the appropriate azole heterocycle Using the methods similar to those described in 1), the example compounds described were obtained.

３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（２００ｍｇ；１．０５ｍｍｏｌ）、４−ブロモヨウドベンゼン（２９７ｍｇ；１．０５ｍｍｏｌ）、Ｋ_２ＣＯ_３（３０２ｍｇ；２．１８ｍｍｏｌ）、ＣｕＩ（２０ｍｇ；０．１１ｍｍｏｌ）およびＮ，Ｎ−ジメチルグリシン（３０ｍｇ；０．２９ｍｍｏｌ）のＤＭＳＯ（４ｍＬ）中撹拌混合物を、１３０℃で５時間３０分加熱した。反応混合物をＤＣＭおよび水間で分配し、有機相をシリカ（メタノールで溶出）により精製し、減圧下で濃縮し、褐色油を得た（４１１ｍｇ）。これを、カラムクロマトグラフィーにより精製して、１−（４−ブロモフェニル）−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾールおよび１−（４−ヨウドフェニル）−３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール（２０５ｍｇ）の混合物を得た。アルゴン雰囲気下、９５ｍｇのこの混合物を無水ＴＨＦ（２ｍＬ）中に溶解し、−７８℃に冷却し、ｎ−ブチルリチウム（ヘキサン中２．５Ｍ、３３０μＬ；０．８２ｍｍｏｌ）を２分にわたって滴下した。１時間撹拌した後、Ｎ，１−ジメチル−Ｎ−（メチルオキシ）−１Ｈ−イミダゾール−２−カルボキサミド（９３ｍｇ；０．５５ｍｍｏｌ）を、冷却した混合物（−７８℃）に加え、反応物をさらに４０分間この温度で撹拌した。反応物を０℃に加温し、この温度で５時間２０分間撹拌した。さらにＮ，１−ジメチル−Ｎ−（メチルオキシ）−１Ｈ−イミダゾール−２−カルボキサミド（５８ｍｇ；０．３４ｍｍｏｌ）を加え、反応物を０℃でさらに１時間撹拌した。反応物を塩酸（１Ｍ、２ｍＬ）によりクエンチし、ＳＣＸカラムクロマトグラフィーにより精製して、白色固体を得た（３２ｍｇ）。これをさらにＭＤＡＰにより精製して、標題化合物を白色固体として得た（１．１４ｍｇ；０．２９％［２工程］）。
ＬＣ／マススペクトル（ＥＳ）：実測値３７５（ＥＳ＋）、保持時間３．４４分；Ｃ_１９Ｈ_１７Ｆ_３Ｎ_４Ｏとして計算値３７４
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤ_３ＯＤ）：１．８０−１．９２（４Ｈ，ｍ），２．６８（２Ｈ，ｂｒ ａｐｐ ｓ），２．８５（２Ｈ，ｂｒ ａｐｐ ｓ），７．２０（１Ｈ，ｄ，Ｊ＝１Ｈｚ），７．４５（１Ｈ，ａｐｐ ｓ），７．７０−７．７５（２Ｈ，ｍ），８．２８−８．３５（２Ｈ，ｍ） Example 112: (1-Methyl-1H-imidazol-2-yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone Acid salt

3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (200 mg; 1.05 mmol), 4-bromoiodobenzene (297 mg; 1.05 mmol), K ₂ CO ₃ (302 mg; 2 .18 mmol), CuI (20 mg; 0.11 mmol) and N, N-dimethylglycine (30 mg; 0.29 mmol) in DMSO (4 mL) were heated at 130 ° C. for 5 h 30 min. The reaction mixture was partitioned between DCM and water and the organic phase was purified on silica (eluting with methanol) and concentrated under reduced pressure to give a brown oil (411 mg). This was purified by column chromatography to give 1- (4-bromophenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole and 1- (4-iodophenyl) A mixture of -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole (205 mg) was obtained. Under an argon atmosphere, 95 mg of this mixture was dissolved in anhydrous THF (2 mL), cooled to −78 ° C., and n-butyllithium (2.5 M in hexane, 330 μL; 0.82 mmol) was added dropwise over 2 minutes. After stirring for 1 hour, N, 1-dimethyl-N- (methyloxy) -1H-imidazole-2-carboxamide (93 mg; 0.55 mmol) was added to the cooled mixture (−78 ° C.) and the reaction was further added. Stir at this temperature for 40 minutes. The reaction was warmed to 0 ° C. and stirred at this temperature for 5 hours and 20 minutes. Further N, 1-dimethyl-N- (methyloxy) -1H-imidazole-2-carboxamide (58 mg; 0.34 mmol) was added and the reaction was stirred at 0 ° C. for an additional hour. The reaction was quenched with hydrochloric acid (1M, 2 mL) and purified by SCX column chromatography to give a white solid (32 mg). This was further purified by MDAP to give the title compound as a white solid (1.14 mg; 0.29% [2 steps]).
LC / Mass Spec (ES): Found 375 (ES +), retention time 3.44 _{min; C 19 H 17 F 3 N} 4 O Calculated 374
¹ H-NMR (400 MHz, CD ₃ OD): 1.80-1.92 (4H, m), 2.68 (2H, br app s), 2.85 (2H, br app s), 7.20 (1H, d, J = 1 Hz), 7.45 (1H, app s), 7.70-7.75 (2H, m), 8.28-8.35 (2H, m)

不活性雰囲気下（Ａｒ）、ＮａＨ（鉱油中６０％、３．８ｍｇ；９５μｍｏｌ）を、Ｎ−｛４−［３−（トリフルオロメチル）−４，５，６，７−テトラヒドロ−１Ｈ−インダゾール−１−イル］フェニル｝−１−ピロリジンカルボキサミド（１７．７ｍｇ；４４μｍｏｌ）の無水ＤＭＦ（１．５ｍＬ）中撹拌溶液に加えた。室温にて１時間撹拌した後、ＭｅＩ（２０μＬ；０．３２ｍｍｏｌ）を加え、反応混合物を２時間１０分この温度で撹拌した。反応物をメタノール性アンモニア（１Ｍ、１ｍＬ）でクエンチし、減圧下で濃縮し、カラムクロマトグラフィーにより精製して、所望の物質を黄色油として得た（１５．４ｍｇ；８４％）。
ＬＣ／マススペクトル（ＥＳ）：実測値３９３（ＥＳ＋）、保持時間３．４６分；Ｃ_２０Ｈ_２３Ｆ_３Ｎ_４Ｏとして計算値３９２
^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）：１．６７−１．７７（４Ｈ，ｍ），１．７７−１．８８（４Ｈ，ｍ），２．６２−２．７６（４Ｈ，ｍ），３．０４−３．１８（４Ｈ，ｍ），３．２６（３Ｈ，ｓ），７．１５−７．２３（２Ｈ，ｍ），７．３ Example 113: N-methyl-N- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide

Under inert atmosphere (Ar), NaH (60% in mineral oil, 3.8 mg; 95 μmol) was added to N- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole. -1-yl] phenyl} -1-pyrrolidinecarboxamide (17.7 mg; 44 μmol) was added to a stirred solution in anhydrous DMF (1.5 mL). After stirring at room temperature for 1 hour, MeI (20 μL; 0.32 mmol) was added and the reaction mixture was stirred at this temperature for 2 hours and 10 minutes. The reaction was quenched with methanolic ammonia (1M, 1 mL), concentrated under reduced pressure and purified by column chromatography to give the desired material as a yellow oil (15.4 mg; 84%).
LC / Mass Spec (ES): Found 393 (ES +), retention time 3.46 _{min; C 20 H 23 F 3 N} 4 O Calculated 392
¹ H-NMR (400 MHz, CDCl ₃ ): 1.67-1.77 (4H, m), 1.77-1.88 (4H, m), 2.62-2.76 (4H, m), 3.04-3.18 (4H, m), 3.26 (3H, s), 7.15-7.23 (2H, m), 7.3

  Example 36 requires the use of [3- (1H-imidazol-1-yl) propyl] methylamine (Naiduet. Al. Bioorganic and Medicinal Chemistry Letters (2004), 14 (22), 5573-5777). .

  Example 38 requires the use of N-methyl-2- (1H-1,2,4-triazol-1-yl) ethanamine (WO 2004/014300).

  Example 40 requires the use of N-methyl-1- (1-methyl-1H-pyrrol-2-yl) methanamine (Raineset. Al. Journal of Heterocyclic Chemistry 7 (1), 223-5; 1970). To do.

Biological Assays The ability of the compounds of the present invention to enhance glutamate receptor-mediated responses is as follows: a) using fluorescent calcium indicator dyes such as FLUO4; It can be determined by measuring the evoked current.

a) Calcium Influx Fluorescence Assay Prepare 384-well plates containing inducible monolayers of HEK293 cells that are stably expressed or transiently transfected with human GluR2 flip (non-edited) AMPA receptor subunits To do. These cells form functional homotetrameric AMPA receptors. Tissue culture medium in the wells is discarded and each well is filled with standard buffer (80 μL) (145 mM NaCl, 5 mM KCl, 1 mM MgCl ₂ , 2 mM CaCl ₂ , 20 mM N- [2-hydroxyethyl] − for stable cell lines. Piperazine-N- [2-ethanesulfonic acid (HEPES), 5.5 mM glucose, pH 7.3) or Na release buffer for transiently transfected cells (145 mM N-methyl-glucamine instead of NaCl) And washed 3 times. Plates are then incubated in the dark with 2 μM FLUO4-AM dye (20 μL) (molecular probe, Netherlands) for 60 minutes at room temperature to allow cellular uptake of FLUO-4AM and then released from the cells. It is converted to FLUO-4 by an intracellular esterase that cannot. After incubation, each well is washed 3 times with buffer (80 μL) (30 μL of buffer remained in each well after washing).

  A compound of the invention (or a target compound such as cyclothiazide) is dissolved in dimethyl sulfoxide (DMSO) at a stock concentration of 10 mM. These solutions are further diluted with DMSO using a Biomek FX (Beckman Coulter) in 384 compound plates. Each dilution (1 μL) is transfected into another compound plate and buffer (50 μL) is added. Agonist stimulation (glutamate) plates are prepared by dissolving sodium glutamate with water to obtain a concentration of 100 mM. The solution is diluted with buffer to obtain a final concentration of 500 μM and dispensed into another 384 well plate (50 μL / well) using Multidrop (Thermolabsystems).

  The cell plate is then transferred into a fluorescence imaging plate based reader [eg, FLIPR384 (Molecular Devices)]. Baseline fluorescence readings are taken for 10-240 seconds, then 10 μL from each plate (concentration range 100 μM to 10 pM) containing compounds of the invention made in standard buffer solution is added (final concentration range 30 μM) ˜3 pM). Read fluorescence over 5 minutes. Add 500 μM glutamic acid solution (10 μL) (final concentration is 100 μM). The fluorescence is then read over 4 minutes. The activity of the compound of the present invention and the target compound is determined by measuring the peak fluorescence after the final addition. Activity is also expressed relative to the increase in fluorescence induced by cyclothiazide in its maximal response (ie, 30 μM or more).

The assay is believed to detect a pEC ₅₀ near the effective limit of 3.5-4.0 due to compound solubility limits. pEC ₅₀ results are generally considered to be +/− 0.3 to be precise. Thus, a compound exhibiting a pEC ₅₀ value within that range from such an assay may indeed have a suitable affinity for the receptor, but also has a low affinity, including a much lower affinity. Yes. One or more readings were taken for each compound.

All Example compounds were screened using the assay described above to obtain an average pEC ₅₀ value measured. All compounds had a pEC ₅₀ average value of 3.5 or higher, and on average showed at least 20% activity of cyclothiazide activity (of its maximal response).

b) Whole-cell voltage-clamped electrophysiological assay The ability of the compounds of the invention to enhance AMPA-subtype glutamate receptor-mediated responses is determined by measuring conserved AMPA-induced currents from rat cultured hippocampal neurons. .

The assay involves the electrophysiological characterization of AMPA receptor positive modulators using rat cultured hippocampal neurons. Extracellular stock _{solution, 145mM NaCl, 2.5mM KCl, 1.2mM} MgCl 2, 1.5mM CaCl 2, 10mM N- [2- hydroxyethyl] - piperazine -N- [2- ethanesulfonic acid (HEPES), Contains pH 7.3 with 10 mM D-glucose, NaOH. The intracellular solution was 80 mM CsCl, 80 mM CsF, 10 mM N- [2-hydroxyethyl] -piperazine-N- [2-ethanesulfonic acid (HEPES), 10 mM ethylene glycol-bis (g-aminoethyl ether) -N, Contains pH 7.3 with N, N ', N, -tetra-acetic acid (EGTA), 14 mM MgATP, 14 mM ditris creatine phosphokinase, 50 U / ml creatine phosphokinase, CsOH. The recording electrode was prepared from two equal length glass capillaries (Clark Electrochemical GC120-F10) using Zeitz Instruments DMZ Universal Puller, program 09, and about 3-6 MΩ when measured in extracellular solution. Resulting in an electrode having the following resistance. The electrode is filled with the internal recording solution and backed. Positive pressure is applied to the electrode that suppresses the mixture of internal and external solutions and assists in forming a high resistance seal when the electrode contacts the cell membrane. A glass coverslip fragment with rat cultured hippocampal neurons is placed in a recording chamber located on the stage of an inverted microscope. The tube at the end of the chamber is used to apply extracellular solution to the bath. Rapid solution exchange uses a fast step perfusion system (Biologic RSC160). Two drain tubes that join together along their length are located near the selected cells so that the outflow from only one tube can pass directly through the cell surface. The motorized stepper can be relocated to the tube so that the outflow from the second drain tube can pass cells that cause a solution exchange at the cell membrane surface within 10-20 ms. Excess bath solution is removed through a tube located at the end of the chamber that connects to the vacuum line.

The predicted cell is located in the center of the field of view of the microscope. The cell recording electrode is placed directly on the membrane surface. A superior manipulator control (Luigs and Neumann, SM-6) is used to lower the electrode while monitoring changes in electrode resistance during delivery of a 5 mV depolarizing pulse until a high resistance seal (Gigaseal) is achieved. Whole cell structure is achieved by removal of small pieces of cell membranes by aspiration just below the recording electrode tip. The cell membrane potential is maintained at -70 mV (voltage fixed) via an electrode (Axopatch 200B integrating patch clamp amplifier, pClamp software, Axon instrument). The test solution is applied using a rapid application system using the following protocol, and changes in inward current are recorded and stored for off-line analysis.
1) The exchange of extracellular solution + 30 μM AMPA (application time 2 seconds, application interval 30 seconds) was repeated from the extracellular solution until the control current measurement was stabilized.
2) Test current-The exchange of extracellular solution + 10 nM compound of the invention from extracellular solution + 10 nM compound of the invention + 30 μM AMPA (application time 2 seconds, application interval 30 seconds) was repeated until the measurement was stable.

  All experiments are performed at room temperature (20-22 ° C.).

The activity of the compounds of the invention is determined by measuring the area under the curve (during the application time of 2 seconds) for a 30 μM AMPA reaction in the presence of the compounds of the invention and the reaction of 30 μM AMPA alone (this Expressed as% of synergism of 30 μM AMPA in the absence of inventive compounds.
The range of average response at 10 nM increased the 30 uM AMPA response by 14-79% and at 10 uM by 42-679%.

Claims (19)

Formula (A):

[Where:
q is 0 or 1;
n is 0, 1 or 2;
X is CR ⁶ R ⁷ and R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are not both methyl at the same time; or , When n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) a C-bonded 5-membered aromatic heterocyclic optionally substituted by methyl A group selected from the group consisting of (iii) NHR ² and (iv) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl; or R ^{2 '} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6 A membered non-aromatic heterocyclic group, wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl _{), C 2-4} alkyl, optionally substituted by one, two or three groups independently selected from the group consisting of halo _{C 1-4} alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2 and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² is a group consisting of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, Selected from the group consisting of C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are the nitrogen atom to which they are attached. With:
(I) a 5-membered aromatic heterocyclic group (wherein independent of the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups selected as above);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) And (iv) a 6-membered non-aromatic heterocyclic group (wherein substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); May be);
Forming a group selected from the group consisting of]
Or a salt or solvate thereof: However, 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl] Phenyl] -1,2,3-thiadiazole-5-carboxamide and salts thereof, or simultaneously, n = 0, m = 1, q = 0, Y = CO and R ¹ are NMe ₂ , pyrrolidinyl, NMeCH ₂ Ph, morpholinyl, _{piperidyl, NHEt, NEt 2, NHMe,} NHCH 2 - _{tetrahydrofuran-2-yl, NH (CH 2) 2 Ph} , NH (CH 2) Ph, selected from NHtBu and NH _{(CH 2)} group consisting of 3 OMe Excluding compounds. Formula (Ie):

[Where:
q is 0 or 1;
n is 0, 1, or 2;
X is CR ⁶ R ⁷ , wherein R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are both methyl at the same time Or, when n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) imidazolyl optionally substituted by methyl, (iii) NHR ² and (iv) Selected from the group consisting of NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl;
R ^{2 ′} and R ³ together with the nitrogen atom to which they are attached:
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are from the group consisting of hydrogen and C _1-4 alkyl) (Optionally selected), optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6-membered A non-aromatic heterocyclic group of the above wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, halo C _1-4 alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2, and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl, and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² consists of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl, and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cyclo Selected from the group consisting of alkyl, C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are attached Together with the nitrogen atom:
(I) a 5-membered aromatic heterocyclic group (independently selected from the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy);
(Iv) 6-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy)
Forming a group selected from the group consisting of]
Or a salt or solvate thereof: wherein n = 0, m = 1, q = 0, Y = CO and R ¹ are NMe ₂ , pyrrolidinyl, NMeCH ₂ Ph, morpholinyl, piperidyl, NHEt _{, NEt 2, NHMe, NHCH 2} - except _{tetrahydrofuran-2-yl, NH (CH 2) 2 Ph} , NH (CH 2) Ph, is selected from NHtBu and NH _{(CH 2)} group consisting of 3 OMe compound. Formula (If):

[Where:
q is 0 or 1;
n is 0, 1, or 2;
X is CR ⁶ R ⁷ , wherein R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are both methyl at the same time Or when n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
(A) (i) when n is 0, m is 1 and Y is CO, R ¹ is (i) C _1-4 alkyl, (ii) C optionally substituted by methyl -Selected from the group consisting of a 5-membered aromatic heterocyclic group, (iii) NHR ² and (iv) NR ^{2 '} R ³ ;
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of ₄ alkyl; or R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are from the group consisting of hydrogen and C _1-4 alkyl) (Optionally selected), optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6-membered A non-aromatic heterocyclic group of the above wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, halo C _1-4 alkyl and keto);
Forming;
(A) (ii) when n is 0, m is 1, and Y is NR ⁸ CO, SO, SO ₂ or NR ⁸ SO ₂ , R ¹ is (i) C _1-4 alkyl, Selected from the group consisting of (ii) NHR ² and (iii) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of ₄ alkyl; or R ^{2 ′} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are from the group consisting of hydrogen and C _1-4 alkyl) (Optionally selected), optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6-membered A non-aromatic heterocyclic group of the above wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently selected from the group consisting of hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of C _2-4 alkyl, halo C _1-4 alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2, and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl, and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached may be combined with a 5-membered aromatic or non-aromatic heterocyclic group or 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto And d) when n is 1 or 2, and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group ( _1-6 alkyl and _{C 3-6} cycloalkyl, and ^NR 11 optionally substituted by one, two or three groups independently selected from the group consisting of ^{R 12} is selected from the group consisting of may also be): Where R ¹¹ is hydrogen and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl, and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6. Selected from the group consisting of cycloalkyl, C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are Nitrogen field Together with:
(I) a 5-membered aromatic heterocyclic group (independently selected from the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); And (iv) a 6-membered non-aromatic heterocyclic group (optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) ;
Forming a group selected from the group consisting of]
In compound represented by or a salt or solvate thereof: where simultaneously, n = 0, m = 1 , q = 0, Y = CO and ^{R 1,:} NMe _2, pyrrolidinyl, NMeCH ₂ Ph, morpholinyl, piperidyl, except _{tetrahydrofuran-2-yl, NH (CH 2) 2 Ph} , NH (CH 2) Ph, the NHtBu and NH _{(CH 2)} a compound selected from the group consisting of _{3 OMe - NHEt, NEt 2,} NHMe, NHCH 2 . N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-ethyl-N-methyl-4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] benzamide N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazol-1-yl] phenyl} -1-propanone 1- [4- (methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazole 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl- 2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1- Loridinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazol-1-yl] phenyl} acetamide N-methyl-N- (2-phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahi Ro-1H-indazol-1-yl] phenyl} acetamide 1-{[4- (1-pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazole 1- {4- [1-methyl-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-dimethyl-3- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3- Oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pi Loridinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl ] Phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl } -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetra Hydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2-thienylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-te Lahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole -1-yl] phenyl} methyl) propanamide N-ethyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} Methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5 {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H- Midazol-1-yl) propyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [ 2- (2-Thienyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- ( 1H-1,2,4-triazol-1-yl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl -N- (1,3-thiazol-2-ylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl- -[2- (1-Methyl-1H-pyrrol-2-yl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- ( 3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N- (2-furanylmethyl) -N-methyl-4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-[(4-fluorophenyl) methyl] -N-methyl-4- [ -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- {4- [1-fluoro-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazole 1- {4- [1,1-difluoro-2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4 , 5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1-yl] phenyl} methyl) methanesulfonamide 1- (4-{[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] methyl} phenyl) -2 -Pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -1-pyrrolidinecarboxamide 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- (1- {4- [3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide N-methyl-N- (1- {4- [3- (trifluorome Til) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide 1- [4- (1-acetyl-2-pyrrolidinyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Ethyl) -2-pyrrolidinone 1- {4-[(1,1-dioxide-2-isothiazolidinyl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazole 2-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propa N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) butanamide N-({4- [3- (tri Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-thiophenecarboxamide N-({4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1 -Yl] phenyl} methyl) acetamide N-methyl-2-phenyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-i Dazol-1-yl] phenyl} methyl) acetamide N- (2-hydroxyethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1 -Yl] benzamide N-methyl-N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (methylamino) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1-({ 4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinol N-methyl- -({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinamine 1- [4- (1-azeti) Dinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1-({4- [3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-azetidinol (3,3-difluorocyclobutyl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazol-1-yl] phenyl} methanone 1- [4- (1H-imidazol-1-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7- Torahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N- ( 1-methylethenyl) -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N-methyl -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide 1- {4-[( 3-methyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [(3-Cyclopropyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl -N- (1-methylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- {4- [2-oxo- 2- (2-Phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide 1- [4- (1,3-oxazol-5-yl) phenyl] -3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (propyloxy) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro- 1H-indazole 1- [4- (1-methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4 -[3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-propanesulfonamide N-({4- [3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide N-({4- [3- (trifluorome ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide 1- [4- (1-pyrrolidinylsulfonyl) phenyl] -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole N- (2-methylpropyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole- 1-yl] benzenesulfonamide 1- [4- (4-morpholinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N- [2- ( Methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonami N- [2- (1-pyrrolidinyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- (tetrahydro- 2-furanylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (1H-imidazol-1-ylmethyl) ) Phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,4-triazol-1-ylmethyl) phenyl] -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-pyrazol-1-ylmethyl) phenyl] -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,3-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4 , 5,6,7-tetrahydro-1H-indazole 1- [4- (2H-1,2,3-triazol-2-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7 -Tetrahydro-1H-indazole 1- {4-[(4-methyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazole 1- {4-[(3,5-dimethyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Sol 3- (trifluoromethyl) -1- (4-{[3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 3- (trifluoromethyl) -1- (4-{[5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -4,5,6,7-tetrahydro-1H-indazole 1 -(4-{[5-Methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H -Indazole 1- (4-{[3-methyl-5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7- Torahydro-1H-indazole 1- {4-[(2-methyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[2- (1-methylethyl) -1H-imidazol-1-yl] methyl} phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-Phenyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [(4-Bromo-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl -1H-imidazol-2-yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone N-methyl-N- {4 -Selected from the group consisting of [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide and its salts and solvates, 4. A compound according to claim 1, 2 or 3. Formula (I) for use as a medicament:

[Where:
q is 0 or 1;
n is 0, 1 or 2;
X is CR ⁶ R ⁷ and R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are not both methyl at the same time; or , When n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _1-4 alkyl and C _2-4 alkenyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) a C-bonded 5-membered aromatic heterocyclic optionally substituted by methyl A group selected from the group consisting of (iii) NHR ² and (iv) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl; or R ^{2 '} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6 A membered non-aromatic heterocyclic group, wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl _{), C 2-4} alkyl, optionally substituted by one, two or three groups independently selected from the group consisting of halo _{C 1-4} alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2 and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² is a group consisting of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, Selected from the group consisting of C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are the nitrogen atom to which they are attached. With:
(I) a 5-membered aromatic heterocyclic group (wherein independent of the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups selected as above);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) And (iv) a 6-membered non-aromatic heterocyclic group (wherein substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); May be);
Forming a group selected from the group consisting of]
Or a salt or solvate thereof: However, 4-methyl-N- [4- [4,5,6,7-tetrahydro-3- (trifluoromethyl) -1H-indazol-1-yl ] Phenyl] -1,2,3-thiadiazole-5-carboxamide and its salts are excluded.   A pharmaceutical composition comprising a compound according to claim 5 and at least one carrier, diluent or excipient. Formula (Ii) for use in the treatment of a disease or condition mediated by a glutamate receptor:

[Where:
q is 0 or 1;
n is 0, 1 or 2;
X is CR ⁶ R ⁷ and R ⁶ and R ⁷ are each independently selected from the group consisting of hydrogen, methyl and fluoro: provided that R ⁶ and R ⁷ are not both methyl at the same time; or , When n is 1, R ⁶ and R ⁷ together with the carbon atom to which they are attached form a three-membered carbocycle;
Y is selected from the group consisting of CO, NR ⁸ CO, SO, SO ₂ and NR ⁸ SO ₂ ;
R ⁸ is selected from the group consisting of hydrogen, C _2-4 alkenyl and C _1-4 alkyl;
m is 0 or 1;
a) when n is 0 and m is 1, R ¹ is (i) C _1-4 alkyl, (ii) a C-bonded 5-membered aromatic heterocyclic optionally substituted by methyl A group selected from the group consisting of (iii) NHR ² and (iv) NR ^{2 ′} R ³ , wherein:
R ² is selected from the group consisting of C _1-6 straight chain alkyl, C _4-6 branched chain alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic heterocyclic group, wherein the phenyl or heterocyclic group is from halo, C _1-4 alkyl and halo C _1-4 alkyl. Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of: when Y is CO, R ² is other than (CH ₂ ) ₂ pyrrolidinyl;
R ^{2 ′} is selected from the group consisting of methyl and ethyl;
R ³ is selected from the group consisting of C _1-6 alkyl and — (CH ₂ ) _p Z (wherein p is 1, 2 or 3);
Z ′ is hydroxy, methoxy, NHMe, phenyl or a 5 or 6 membered non-aromatic or aromatic heterocyclic group, which phenyl or heterocyclic group is halo, C _1-4 alkyl and halo C ₁ Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of _-4 alkyl; or R ^{2 '} and R ³ are taken together with the nitrogen atom to which they are attached. :
(I) a 4- or 5-membered non-aromatic heterocyclic group (wherein the ring is halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are independently hydrogen and C _1-4 alkyl Optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of haloC _1-4 alkyl, and keto); or (ii) 6 A membered non-aromatic heterocyclic group, wherein the ring is independently selected from the group consisting of halo, hydroxy, NR ¹³ R ^14, wherein R ¹³ and R ¹⁴ are hydrogen and C _1-4 alkyl _{), C 2-4} alkyl, optionally substituted by one, two or three groups independently selected from the group consisting of halo _{C 1-4} alkyl and keto);
Forming;
b) When n and m are both 0 at the same time, R ¹ is:
C _1-6 alkoxy;
1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto, bonded through a carbon atom. A monocyclic saturated or partially unsaturated 5- or 6-membered heterocyclic group optionally substituted by
May be substituted by 1, 2 or 3 groups independently selected from the group consisting of C _1-4 alkyl, C (O) C _1-4 alkyl, haloC _1-4 alkyl, halo and keto Good N-linked pyrrolidinyl; and oxazolyl or imidazolyl optionally substituted by C _1-4 alkyl;
Selected from the group consisting of;
c) when n is 1 or 2 and m is 1, R ¹ is selected from the group consisting of C _1-4 alkyl, benzyl, cyclopropyl, thienyl and NR ⁹ R ¹⁰ , wherein:
R ⁹ is selected from the group consisting of hydrogen and C _1-4 alkyl, and R ¹⁰ is C _1-6 linear alkyl, C _3-6 cycloalkyl and — (CH ₂ ) _p Z where p is Selected from the group consisting of 1, 2 or 3;
Z is phenyl or a 5 or 6 membered heterocyclic group, wherein the phenyl or heterocyclic group is independently selected from the group consisting of halo and C _1-4 alkyl. Optionally substituted by a group; or R ⁹ and R ¹⁰ together with the nitrogen atom to which they are attached, a 5-membered aromatic or non-aromatic heterocyclic group or a 6-membered non-aromatic 1, 2 or 3 independently selected from the group consisting of C _1-4 alkyl, halo, phenyl and (if non-aromatic ring) keto Optionally substituted by a group of
d) when n is 1 or 2 and m is 0, R ¹ is a cyano, hydroxy, NH ₂ , C-bonded 5-membered aromatic heterocyclic group (C _1-6 alkyl and C _3- Selected from the group consisting of ₆ cycloalkyl, and optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of NR ¹¹ R ¹² , wherein:
R ¹¹ is hydrogen and R ¹² is a group consisting of SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, C (O) C _1-4 alkyl and C (O) C _2-4 alkenyl. Or R ¹¹ is selected from the group consisting of C _1-4 alkyl and C _2-4 alkenyl, and R ¹² is SO ₂ C _1-4 alkyl, SO ₂ C _3-6 cycloalkyl, Selected from the group consisting of C (O) C _1-4 alkyl, C (O) phenyl and C (O) C _2-4 alkenyl, or R ¹¹ and R ¹² are the nitrogen atom to which they are attached. With:
(I) a 5-membered aromatic heterocyclic group (wherein independent of the group consisting of C _1-4 alkyl, halo, halo C _1-4 alkyl, hydroxy, C _3-6 cycloalkyl and C _1-4 alkoxy) Optionally substituted by 1 or 2 groups selected as above);
(Ii) imidazolyl substituted by phenyl;
(Iii) a 5-membered non-aromatic heterocyclic group (which may be substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy) And (iv) a 6-membered non-aromatic heterocyclic group (wherein substituted by 1, 2 or 3 groups independently selected from the group consisting of keto, hydroxy and C _1-4 alkoxy); May be);
Forming a group selected from the group consisting of]
Or a salt or solvate thereof. N, N-dimethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- (1-pyrrolidinylcarbonyl) phenyl ] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N- (phenylmethyl) -4- [3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] benzamide N-ethyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Benzamide N-butyl-N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methy -N- (2-Phenylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N, N-dimethyl-4- [3 -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- {4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] phenyl} ethanone 1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1- Propanone 1- [4- (methylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [3- (trifluoro Til) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -2-propanone N, N-dimethyl-2- {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4, 5,6,7-Tetrahydro-1H-indazole N-ethyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl Phenyl} acetamide N-methyl-N- (phenylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] Nyl} acetamide N-butyl-N-methyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl- N- (2-phenylethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide 1-{[4- (1-Pyrrolidinylcarbonyl) phenyl] methyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1-methyl-2-oxo-2- (1-Pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-dimethyl-3- {4- [3- (trif Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} propanamide 1- {4- [3-oxo-3- (1-pyrrolidinyl) propyl] phenyl} -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1- (1-pyrrolidinylcarbonyl) cyclopropyl] phenyl} -3- (trifluoromethyl) -4, 5,6,7-tetrahydro-1H-indazole 1- {4- [2-oxo-2- (1-piperidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro -1H-indazole 1- {4- [2- (3,3-difluoro-1-pyrrolidinyl) -2-oxoethyl] phenyl} -3- (trifluoromethyl) -4,5 6,7-Tetrahydro-1H-indazole N-methyl-N-propyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl } Acetamide N-cyclopentyl-2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide N-methyl-N- (2- Thienylmethyl) -2- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetamide {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} acetonitrile {4- [3- (trifluoromethyl) -4,5,6,7 Tetrahydro-1H-indazol-1-yl] phenyl} methanol N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] Phenyl} methyl) acetamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-pyrrolidinone N-methyl- N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-ethyl-N-({4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide 1-({4- [3- (Trif Olomethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2-piperidinone 1-methyl-5- {4- [3- (trifluoromethyl) -4,5 , 6,7-Tetrahydro-1H-indazol-1-yl] phenyl} -2-pyrrolidinone N- [3- (1H-imidazol-1-yl) propyl] -N-methyl-4- [3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (2-thienyl) ethyl] -4- [3- (trifluoromethyl)- 4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamido N-methyl-N- [2- (1H-1,2,4-triazol-1-yl) ethyl] -4- [3 − Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (1,3-thiazol-2-ylmethyl) -4- [3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (1-methyl-1H-pyrrol-2-yl) ethyl] -4- [ 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (2-thienylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- (3-pyridinylmethyl) -4- [3- (trifluoromethyl) -4,5 6,7-tetrahydro-1H-indazol-1-yl] benzamide N- (2-furanylmethyl) -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazol-1-yl] benzamide N-[(4-fluorophenyl) methyl] -N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1- Yl] benzamide 1- [4- (4-morpholinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- {4- [1-fluoro- 2-oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4- [1,1-difluoro-2 -Oxo-2- (1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-methyl-N-({4- [3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) methanesulfonamide 1- (4-{[3- (trifluoromethyl) -4,5,6 , 7-Tetrahydro-1H-indazol-1-yl] methyl} phenyl) -2-pyrrolidinone N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahi Dro-1H-indazol-1-yl] phenyl} methyl) -1-pyrrolidinecarboxamide 5- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} -2-pyrrolidinone N- (1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide N-methyl -N- (1- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) acetamide 1- [4- (1-acetyl -2-pyrrolidinyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (2- {4- [3- (trifluoro) Methyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} ethyl) -2-pyrrolidinone 1- {4-[(1,1-dioxide-2-isothiazolidinyl) methyl ] Phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 2-methyl-N-({4- [3- (trifluoromethyl) -4,5,6 7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} methyl) butanamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) -2 Thiophenecarboxamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) propanamide N-({4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide N-methyl-2-phenyl-N-({4- [3- (trifluoromethyl ) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) acetamide N- (2-hydroxyethyl) -N-methyl-4- [3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (methyloxy) ethyl] -4- [3- (trif Olomethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide N-methyl-N- [2- (methylamino) ethyl] -4- [3- (trifluoromethyl) -4 , 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Phenyl} carbonyl) -3-pyrrolidinol N-methyl-1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-pyrrolidinamine 1- [4- (1-azetidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-in Sol 1-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} carbonyl) -3-azetidinol (3,3-difluorocyclobutyl ) {4- [3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methanone 1- [4- (1H-imidazol-1-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole -1-yl] phenyl} methyl) -2-propenamide N- (1-methylethenyl) -N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahi Dro-1H-indazol-1-yl] phenyl} methyl) -2-propenamide N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H- Indazol-1-yl] phenyl} methyl) -2-propenamide 1- {4-[(3-methyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- (trifluoro Methyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl) methyl] phenyl} -3- ( Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N-ethyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl ] Benzamide N-methyl-N- (1-methylethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzamide 1- [4- ( 1-piperidinylcarbonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N, N-diethyl-4- [3- (trifluoromethyl) -4, 5,6,7-Tetrahydro-1H-indazol-1-yl] benzamide N-methyl-4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] Benzamide 1- {4- [2-oxo-2- (2-phenyl-1-pyrrolidinyl) ethyl] phenyl} -3- (trifluoromethyl) -4,5,6,7-tetrahydride -1H-indazole N-methyl-N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) benzamide 1- [4 -(1,3-oxazol-5-yl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (propyloxy) phenyl] -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1-methyl-1H-imidazol-4-yl) phenyl] -3- (trifluoromethyl) -4, 5,6,7-Tetrahydro-1H-indazole N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] pheni } Methyl) -2-propanesulfonamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopropanesulfonamide N-({4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} methyl) cyclopentanesulfonamide 1- [4- (1-pyrrole) Dinylsulfonyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N- (2-methylpropyl) -4- [3- (trifluoromethyl) -4, 5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (4-morpholinylsulfonyl) phenyl] -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole N- [2- (methyloxy) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7- Tetrahydro-1H-indazol-1-yl] benzenesulfonamide N- [2- (1-pyrrolidinyl) ethyl] -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole -1-yl] benzenesulfonamide N- (tetrahydro-2-furanylmethyl) -4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] benzenesulfonamide 1- [4- (1H-imidazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-i Dandol 1- [4- (1H-1,2,4-triazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-pyrazol-1-ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (1H-1,2,3-triazole-1) -Ylmethyl) phenyl] -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- [4- (2H-1,2,3-triazol-2-ylmethyl) phenyl]- 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-methyl-1H-pyrazol-1-yl) methyl] phenyl}- -(Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(3,5-dimethyl-1H-pyrazol-1-yl) methyl] phenyl} -3- (tri Fluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 3- (trifluoromethyl) -1- (4-{[3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} Phenyl) -4,5,6,7-tetrahydro-1H-indazole 3- (trifluoromethyl) -1- (4-{[5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl ) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} phenyl) 3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[3-methyl-5- (trifluoromethyl) -1H-pyrazol-1-yl] methyl} Phenyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(2-methyl-1H-imidazol-1-yl) methyl] phenyl} -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- (4-{[2- (1-methylethyl) -1H-imidazol-1-yl] methyl} phenyl) -3- (Trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-phenyl-1H-imidazol-1-yl) methyl] phenyl} -3- (trif Olomethyl) -4,5,6,7-tetrahydro-1H-indazole 1- {4-[(4-bromo-1H-pyrazol-1-yl) methyl] phenyl} -3- (trifluoromethyl) -4, 5,6,7-Tetrahydro-1H-indazole N-methyl-1H-imidazol-2-yl) {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole-1 -Yl] phenyl} methanone N-methyl-N- {4- [3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazol-1-yl] phenyl} -1-pyrrolidinecarboxamide and 8. A compound according to claim 5 or claim 7 selected from the group consisting of its salts and solvates.   9. A compound according to claim 7 or claim 8, wherein the disease is schizophrenia.   9. A compound according to claim 7 or claim 8, wherein the disease is cognitive impairment.   Use of a compound according to any one of claims 5, 7 or 8 in the manufacture of a medicament for the treatment of a disease or condition mediated by reduced or imbalanced glutamate receptor function.   12. Use according to claim 11, wherein the disease is schizophrenia.   12. Use according to claim 11, wherein the disease is cognitive impairment.   A method for the treatment of a disease or condition mediated by reduced or unbalanced glutamate receptor function, comprising administering an effective amount of a compound according to any one of claims 5, 6 or 8.   15. A method according to claim 14, wherein the disease is schizophrenia.   15. A method according to claim 14, wherein the disease is cognitive dysfunction.   A combination product comprising a compound according to any one of claims 5 to 8 and an antipsychotic. Formulas (V), (VII) and (X):

[Wherein n is 0, 1 or 2, Hal is halogen, and R is C _1-4 alkyl]
And a compound selected from the group consisting of salts and solvates thereof. A method for producing a compound represented by the formula (Ii) according to claim 7, wherein the compound has the formula (II):

[Wherein X ′ is a leaving group, and X, Y, q, m, n and R ¹ are as defined in the formula (Ig) of claim 8.]
And 3- (trifluoromethyl) -4,5,6,7-tetrahydro-1H-indazole; and then optionally:
-Removing any protecting groups; and / or-converting a compound of formula (Ii) or a salt or solvate thereof into another compound of formula (Ii) or a salt or solvate thereof. To do;
Including methods.